Circulating and Tumor-Infiltrating Myeloid Cells Predict Survival in Human Pleural Mesothelioma
|
|
- Abel Baker
- 8 years ago
- Views:
Transcription
1 Circulating and Tumor-Infiltrating Myeloid Cells Predict Survival in Human Pleural Mesothelioma Bryan M. Burt, MD 1 ; Scott J. Rodig, MD, PhD 2 ; Tamara R. Tilleman, MD, PhD 1 ; Andrew W. Elbardissi, MD, MPH 1 ; Raphael Bueno, MD 1 ; and David J. Sugarbaker, MD 1 BACKGROUND: Malignant pleural mesothelioma (MPM) tumor cells produce copious amounts of myeloid cell-stimulating factors. The current study examined the prognostic significance of circulating monocytes and tumor-infiltrating macrophages on overall survival in patients with MPM. METHODS: The authors retrospectively reviewed 667 patients with MPM who underwent cytoreductive surgery at the Brigham and Women s Hospital in Boston, Massachusetts between 1989 and Kaplan-Meier and Cox proportional hazards models were used to determine the impact of preoperative circulating monocytes on overall survival. Immunohistochemical staining for CD68 was performed on a tissue microarray of MPM tumors from 52 patients undergoing cytoreductive surgery. The phenotype of circulating monocytes and tumor-infiltrating macrophages in 7 additional patients was determined by flow cytometry. RESULTS: The median survival for all patients was 13.4 months, and 35% of patients had tumors of nonepithelial histology. For patients with nonepithelial compared with epithelial tumors, survival was significantly worse (9.3 months vs 16.6 months; P <.0001), the number of monocytes was significantly higher ( cells/ll vs cells/ll; P ¼.002), and higher monocyte counts were associated with higher tumor stage. Increasing monocyte counts were correlated with poor survival for all patients with MPM. Within MPM tumors, macrophages comprised 27% 9% of the tumor area and demonstrated an immunosuppressive phenotype with high expression of CD163, CD206, and interleukin-4 receptor a. The degree of macrophage infiltration was found to be negatively correlated with survival in patients with nonepithelial (P ¼.008) but not those with epithelial (P ¼.7) MPM, independent of disease stage. CONCLU- SIONS: Higher numbers of circulating monocytes are associated with poor survival in all patients with MPM and higher densities of tumor-infiltrating macrophages are associated with poor survival in patients with nonepithelial MPM. Both may enable a novel target for immunotherapy. Cancer 2011;117: VC 2011 American Cancer Society. KEYWORDS: mesothelioma, monocytes, macrophages, tumor-infiltrating macrophages, tumor-associated macrophages, interleukin-4 receptor a. Malignant pleural mesothelioma (MPM) is a highly fatal tumor arising from the mesothelial cell lining of the pleura. Although its proclivity for distant metastasis is low, MPM is highly invasive to surrounding tissues and results in failure of adjacent organs. The median survival of patients with MPM is only 4 to 19 months 1-3 and epidemiologic studies suggest that its worldwide incidence continues to rise. 4 MPM is often unresponsive to chemotherapy or radiotherapy, although select patients will benefit from multimodality therapy that incorporates cytoreductive surgery, chemotherapy, and radiation. 3 In recent years, it has become evident that chronic inflammation predisposes individuals to cancer. In the tumor microenvironment, inflammation promotes the proliferation and survival of malignant cells, supports angiogenesis and metastasis, and subverts immune reactions and responses to chemotherapy. 5 Although the mechanisms of carcinogenesis in MPM are incompletely understood, they clearly overlie a background of smoldering inflammation. Occupational exposure to asbestos is the cause of MPM in approximately 80% of individuals with this disease and there is a long latency period between the time of initial exposure and diagnosis, ranging from 20 years to 50 years. 6 In animal models, asbestos Corresponding author: David J. Sugarbaker, MD, Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115; Fax: (617) ; dsugarbaker@partners.org 1 Division of Thoracic Surgery, The Brigham and Women s Hospital, Boston, Massachusetts; 2 Department of Pathology, The Brigham and Women s Hospital, Boston, Massachusetts We thank Dr. Christina Wei for her assistance with tissue processing and flow cytometry. DOI: /cncr.26143, Received: August 28, 2010; Revised: January 9, 2011; Accepted: March 2, 2011, Published online April 26, 2011 in Wiley Online Library (wileyonlinelibrary.com) 5234 Cancer November 15, 2011
2 Myeloid Cells in MPM Predict Survival/Burt et al causes an influx of mononuclear phagocytes into the tumor that internalize asbestos fibers. In response to asbestos, these phagocytes as well as normal mesothelial cells release tumor necrosis factor (TNF)-a and other proinflammatory cytokines that promote malignant transformation of the mesothelium through NK-jB dependent mechanisms. 7,8 In humans, the inflammatory response of MPM tumors is demonstrated by the presence of massive leukocyte infiltrates, comprised mainly of macrophages and CD4 and CD8 T cells. 9,10 Monocytes originate in the bone marrow from pluripotent stem cells. After several stages of development, they are released into the circulation and differentiate into macrophages upon becoming resident in tissues. A high number of circulating monocytes has been associated with poor overall and cancer-related survival in several human malignancies Normal human mesothelial cells and established human MPM cell lines produce copious amounts of hematopoietic cytokines, including interleukin (IL)-6, IL- 8, macrophage inflammatory protein-1, granulocyte-colony stimulating factor, and granulocyte-macrophage-colony stimulating factor. 17,18 These cytokines provide chemotactic and stimulatory signals to immune cells of the myeloid lineage and recruit monocytes to the tumor mass, where they differentiate into macrophages. Macrophages infiltrate several human cancers and, depending on the type of malignancy, may be positively or negatively associated with survival. 19 In mice, tumor-associated macrophages (TAM) promote tumor progression 20 and both murine and human TAM have been shown to possess immunosuppressive function To our knowledge, the association between monocytes and macrophages and clinical outcome is unknown in patients with MPM. In the current study, we set out to determine the prognostic significance of circulating blood monocytes and tumor-infiltrating macrophages in patients with MPM. Table 1. The Brigham and Women s Hospital Staging System for MPM 3 Stage I II III IV Description Disease completely resected within the capsule of the parietal pleura without adenopathy: ipsilateral pleura, lung, pericardium, diaphragm, or chest wall disease limited to previous biopsy sites All of stage I with positive resection margins and/or intrapleural adenopathy Local extension of disease into the chest wall or mediastinum, heart, or through diaphragm or peritoneum, or with extrapleural lymph node involvement Distant metastatic disease Abbreviation: MPM, malignant pleural mesothelioma. MATERIALS AND METHODS Patients In accordance with our institution s institutional review board (IRB), we retrospectively reviewed 667 patients with MPM who underwent cytoreductive surgery from 1989 through Data were obtained from the prospectively maintained International Mesothelioma Program patient data registry and included age, gender, procedure, laterality, pathology, stage of disease according to the Brigham and Women s Hospital (BWH) 3 (Table 1) and TNM staging systems, and overall survival. Preoperative monocyte counts and white blood cell counts (WBC) were determined from the complete blood count and the automated differential drawn within 90 days before surgery. Immunohistochemistry Immunostaining was performed on a tissue microarray (TMA) of 58 resectable MPM tumors that was constructed as previously described. 24 Each tumor was represented in duplicate or quadruplicate cores. Six patients were excluded because of damage to their respective cores, resulting in a sample size of 52. Briefly, the TMA slides were soaked in xylene, passed through graded alcohols, and placed in distilled water. Slides were then pretreated with citrate buffer in a steam pressure cooker (Decloaking Chamber; BioCare Medical, Walnut Creek, Calif) as per the manufacturer s instructions followed by washing in distilled water. All further steps were performed at room temperature in a hydrated chamber. Slides were pretreated with peroxidase block (Dako, Carpinteria, Calif) for 5 minutes to quench endogenous peroxidase activity. A mouse antihuman CD68 antibody (clone PG-M1, Catalog #M0876; Dako) or rabbit antihuman CD3 antibody (Catalog #A0452; Dako) was applied at a dilution of 1:200 in Dako diluent for 1 hour. Slides were washed in 50-mM of Tris-Cl (ph 7.4)anddetectedwiththemouseEnVisionþ kit (Dako) as per the manufacturer s instructions. After further washing, immunoperoxidase staining was developed using a 3,3 0 -diaminobenzidine (DAB) chromogen (Dako) and counterstained with hematoxylin. Image Analysis Slides stained for CD68 and CD3 were scanned at 200 magnification using an Aperio ScanScope XT workstation (Aperio Technology, Inc, Vista, Calif). Images were visualized and annotated using ImageScope software Cancer November 15,
3 Table 2. Monocyte Cohort Patient Characteristics a Variable All Histologies Epithelial Nonepithelial P (n 5 667) (n 5 432) (n 5 235) Age, y Male 531 (79.6) 323 (74.8) 208 (88.5) <.001 Right hemithorax 395 (59.2) 246 (56.9) 149 (63.4).12 EPP 481 (72.1) 320 (74.1) 161 (68.5).13 Epithelial cell type 432 (64.8) BWH stage n ¼ 475 n ¼ 315 n ¼ I 29 (6.1) 19 (6.0) 10 (6.3) II 168 (35.4) 109 (34.6) 59 (36.9) III 278 (58.5) 187 (59.4) 91 (56.9) TNM stage n ¼ 471 n ¼ 313 n ¼ I 13 (2.8) 10 (3.2) 3 (1.9) II 51 (10.8) 32 (10.2) 19 (12.0) III 304 (64.5) 206 (65.8) 98 (62.0) IV 103 (21.9) 65 (20.8) 38 (24.1) Median survival, mo <.0001 WBC, cells/ll Monocytes, cells/ll Lymphocytes, cells/ll Neutrophils, cells/ll Abbreviations: BWH, Brigham and Women s Hospital; EPP, extrapleural pneumonectomy; WBC, white blood cell count. a Data are represented as the mean the standard deviation (%). (version ; Aperio Technology). In a blinded fashion, a pathologist (S.R.) identified and annotated areas of tumor as regions of interest (ROI) using standard ImageScope software functions. The ROIs were then analyzed using a standard analysis algorithm to quantitate the percentage of the annotated area that was positive for staining (color deconvolution version 9.0; Aperio Technology). The resulting data were the percentage of the ROI that stained positively for the macrophage marker CD68 or the T-cell identifier CD3. Scores from duplicate or quadruplicate cores for each tumor were averaged. Flow Cytometry Under an IRB-approved tissue collection protocol, tumor and matched blood samples were collected on the day of surgery from 7 patients undergoing cytoreductive surgery at the BWH. Peripheral blood mononuclear cells (PBMCs) were isolated by density centrifugation over Ficoll-Paque Plus (GE Healthcare; Pittsburgh, Pa). Tumor tissue was minced into small fragments in cold Hank s balanced salt solution and digested at 37 C for 3 hours in RPMI containing 1 mg/ml of collagenase D (Roche Diagnostics, Indianapolis, Ind) and 100 lg/ml of DNAse (Qiagen, Germantown, Md). After passage through 70-lm and 450-lm filters, the suspension was layered over Ficoll, spun at 1000 g for 20 minutes, and then washed. Immunophenotypic analysis of cells was performed using multicolor flow cytometry on an LSRII flow cytometer (BD Biosciences, San Jose, Calif). Antibodies used for cell analysis included V450-CD45 (clone H130), PE-CD14 (M5E2), APC-CD14 (M5E2), PE-CD163 (GHI/61), APC-CD206 (19.2), APC-cy7-HLA-DR (L243), FITC- CD80 (L307.4), and APC-CD86 (IT2.2), all from BD Biosciences, and APC-IL-4Ra (25463) from R&D Systems (Minneapolis, Minn). Unstained cells and immunoglobulin isotype controls were used to set gates. Flow cytometry data were analyzed with FlowJo software (Tree Star Inc, Ashland, Ore). Statistical Analysis Preoperative monocyte count and percentage intratumoral CD68 and CD3 staining were evaluated in histological subtype-specific analyses for epithelial and nonepithelial tumors. Statistical analysis was performed using JMP statistical software (version 8.0; SAS Institute Inc, Cary, NC). Quantitative variables were expressed as the mean the standard deviation. Differences between groups of continuous variables were tested using the Wilcoxon rank sum test and the chi-square test was used to compare categorical variables. Actuarial survival was calculated according to the Kaplan-Meier method, and differences in survival were tested for significance using the log-rank test. Cox proportional hazards modeling was used to examine the relation between monocyte count as a 5236 Cancer November 15, 2011
4 Myeloid Cells in MPM Predict Survival/Burt et al Figure 1. High preoperative monocyte counts are associated with worse overall survival in patients with malignant pleural mesothelioma. (A) Kaplan-Meier survival estimates are shown for the epithelial (n ¼ 432) and nonepithelial (n ¼ 235) groups. For patients with (B) all (n ¼ 667), (C) epithelial (n ¼ 432), and (D) nonepithelial (n ¼ 235) histologies, Kaplan-Meier survival estimates are shown for the preoperative monocyte count separated into quartile groups. continuous variable and overall survival and to estimate 95% confidence intervals. In addition, a Cox proportional hazards model was used to compare the long-term survival based on the number of macrophages using a baseline survival function estimate derived from the Kalbfleisch-Prentice estimator. 25,26 This derived survival function was subsequently used to create long-term survival plots. P values <.05 were considered statistically significant. RESULTS High Preoperative Circulating Monocyte Counts Are Associated With Poor Overall Survival in MPM The clinical and pathologic characteristics of 667 patients who underwent cytoreductive surgery with either extrapleural pneumonectomy (EPP) or pleurectomy and decorticationareshownintable2.approximately65%(n¼ 432) of the patients had epithelial histology, and this histology was associated with better overall survival compared with nonepithelial histology (16.6 months vs 9.3 months;, P <.0001) (Table 2) (Fig. 1A). Patients in the nonepithelial group were of slightly older age and were comprised of Table 3. Association Between Monocytes and Survival HR (95% CI); P All (n ¼ 667) 3.98 ( ); <.0001 Epithelial (n ¼ 432) 2.87 ( );.0003 Nonepithelial (n ¼ 235) 4.63 ( ); <.001 Abbreviations: 95% CI, 95% confidence interval; HR, hazard ratio. a slightly greater number of males. There was no difference in the BWH or TNM stage of disease in patients in the epithelial and nonepithelial groups. The number of preoperative circulating monocytes and the total WBC was higher in the nonepithelial histology group. Higher preoperative monocyte counts were found to be negatively correlated with overall survival in all patients with mesothelioma regardless of histology when analyzed using the Kaplan-Meier survival estimates (Figs. 1B-1D) and Cox proportional hazards methods (Table 3). Patients With Advanced Stage Nonepithelial MPM Have Higher Preoperative Monocyte Counts Complete pathologic staging data are determinable only for patients who undergo EPP. Staging information was Cancer November 15,
5 Figure 2. Patients with advanced stage, nonepithelial malignant pleural mesothelioma have higher preoperative monocyte counts. The preoperative monocyte counts for each Brigham and Women s Hospital stage of disease are shown for patients with (A) all (n ¼ 667), (B) epithelial (n ¼ 432), and (C) nonepithelial (n ¼ 235) histologies. available for 98% of the 481 patients who underwent EPP in the current study. Of this cohort, a higher BWH and TNM stage was found to be correlated with higher monocyte counts for patients in the nonepithelial histology group but not patients in the epithelial histology group (Fig. 2) (data not shown). Despite this correlation, a high monocyte count remained a negative predictor of survival when adjusted for BWH or TNM stage (Table 4) (data not shown). Epithelial and Nonepithelial MPM Are Heavily Infiltrated by Macrophages To evaluate the degree of macrophage infiltration within mesothelioma tumor tissues, we stained our TMA for CD68, a reliable macrophage-identifying antigen. The characteristics of this group are shown in Table 5. We found, in both epithelial and nonepithelial MPM, that macrophages comprised a major percentage of the cellular infiltrate on tissue sections, accounting for 27% 9% of the tumor area. Similarly, using flow cytometry of tumor mononuclear cell suspensions, 28% 8% of all immune cells were macrophages. There was no difference with regard to the degree of macrophage infiltration between epithelial and nonepithelial histology (Table 5) (Fig. 3), and the density of infiltrating macrophages was not found to correlate with BWH stage (Fig. 4) or TNM stage (data not shown). Tumor-Infiltrating Macrophages in MPM Exhibit an Immunoregulatory (M2) Phenotype To determine the phenotype of tumor-infiltrating macrophages of MPM, we performed flow cytometry on mononuclear cell suspensions freshly isolated from tumor and matched blood samples from 7 patients with MPM (Fig. 5). Tumor-infiltrating macrophages displayed a high level of scavenger receptors CD163 and CD206, and also expressed high levels of IL-4 receptor a (IL-4Ra). Table 4. Association Between Monocytes and Survival Unadjusted and Adjusted for BWH Stage Unadjusted HR (95% CI); P Adjusted All (n ¼ 475) 3.64 ( ); < ( ); <.0001 Epithelial (n ¼ 315) 2.81 ( ); ( );.007 Nonepithelial (n ¼ 160) 4.59 ( ); < ( );.001 Abbreviations: 95% CI, 95% confidence interval; BWH, Brigham and Women s Hospital; HR, hazard ratio. Although MPM tumor-infiltrating macrophages expressed high levels of the major histocompatibility complex class II molecule human leukocyte antigen complex DR (HLA-DR), only low or modest levels of the costimulatory molecules CD80 and CD86 were present. There was no difference in the mean fluorescence index in any of these markers on tumor-infiltrating macrophages between patients with epithelial (n ¼ 3) and nonepithelial (n ¼ 4) tumors (data not shown). The Density of Tumor-Infiltrating Macrophages Is Negatively Correlated With Survival in Nonepithelial MPM Given the association between high monocyte count and poor survival, the high density of tumor-infiltrating macrophages within the tumor, and the immunoregulatory phenotype of MPM tumor-infiltrating macrophages, we examined the impact of the macrophage infiltrate on overall survival. For patients with nonepithelial histology, those with a higher density of tumor-infiltrating macrophages demonstrated significantly worse survival than those with a lower density of tumor-infiltrating macrophages, independent of BWH stage (Fig. 6) (Table 6) or TNM stage (data not shown). For patients with epithelial histology, there was no correlation noted between the 5238 Cancer November 15, 2011
6 Myeloid Cells in MPM Predict Survival/Burt et al Table 5. Patient Characteristics of the Macrophage Cohort a Variable All Histologies Epithelial Nonepithelial (n 5 52) (n 5 34) (n 5 18) P Age, y Male 45 (86.5) 30 (88.2) 15 (83.3).84 Right hemithorax 31 (59.6) 21 (61.8) 10 (55.6).94 Epithelial cell type 37 (71.2) BWH stage I 1 (1.9) 0 (0.0) 1 (5.6).35 II 23 (44.2) 16 (47.1) 7 (38.9) III 28 (53.8) 18 (52.9) 10 (55.6) TNM stage I 0 (0.0) 0 (0.0) 0 (0.0).99 II 5 (9.6) 3 (8.8) 2 (11.1) III 36 (69.2) 24 (70.6) 12 (66.7) IV 11 (21.2) 7 (20.6) 4 (22.2) Median survival, mo Infiltrating CD68 þ cells, % Abbreviations: BWH, Brigham and Women s Hospital; þ, positive. a Data are represented as the mean the standard deviation (%). Figure 3. Epithelial and nonepithelial malignant pleural mesothelioma tumor tissues are heavily infiltrated with macrophages. (A) Representative tumor sections of low and high CD68 staining are shown for epithelial and nonepithelial histologies. (B) The percentage of tumor area demonstrating positive staining (þ) for CD68 was compared in the epithelial (n ¼ 34) and nonepithelial (n ¼ 18) groups.
7 Figure 4. The percentage of tumor area demonstrating positive staining (þ) for CD68 in malignant pleural mesothelioma was not found to be correlated with the Brigham and Women s Hospital stage of disease. The stage-specific distribution of CD68 þ cells is shown for (A) all, (B) epithelial, and (C) nonepithelial histologies. Figure 5. Tumor-infiltrating macrophages (Mac) in malignant pleural mesothelioma have an immunoregulatory (M2) phenotype. The cell surface phenotype of tumor-infiltrating macrophages was determined by flow cytometry on freshly isolated mononuclear cell suspensions (Mono) from tumor tissue and matched blood samples from 7 patients. (A) A representative tumor-infiltrating macrophage cell surface phenotype from 1 patient is shown. Panel B shows summary data using the mean fluorescence index (MFI). The contour plots were gated on live cells that were CD45 þ CD14 þ. IL-4Ra indicates interleukin-4 receptor a; HLA- DR, human leukocyte antigen complex DR. macrophage infiltrate and survival. It is interesting to note that a similar finding was noted for CD3-positive (CD3 þ ) tumor-infiltrating T cells; a higher density of CD3 þ T cells was found to be correlated with worse overall survival in patients with nonepithelial MPM, but not those with epithelial MPM (Table 7). DISCUSSION In the tumor microenvironment, interaction among tumor cells, immune cells, stromal cells, and the extracellular matrix is vital to tumor progression. 5 The immunologic cellular infiltrates in human tumors, particularly cytotoxic and memory T cells, independently predict cancer-related survival. In fact, these indices are more sensitive than current histological methods for the estimation of survival in patients with colorectal cancer. 27,28 It has been known for some time that MPM tumors contain an abundance of intratumoral leukocytes, 29 but it is only recently that the composition and phenotype of these cells is being unveiled. Anraku et al demonstrated improved overall survival in patients with MPM tumors that contained a high number of tumor-infiltrating CD8 T cells. 9 In addition, using immunohistochemical stains on Cancer November 15, 2011
8 Myeloid Cells in MPM Predict Survival/Burt et al Figure 6. The percentage of tumor area comprised of CD68-positive macrophages was found to be negatively correlated with survival in patients with nonepithelial malignant pleural mesothelioma (MPM). Survival curves for patients with macrophage staining at or above the median or less than the median are shown for (A) epithelial (median, 27.5%) and (B) nonepithelial (median, 27.5%) MPM groups. HR indicates hazard ratio. Table 6. Association Between Tumor-Infiltrating Macrophages and Survival Unadjusted and Adjusted for BWH Stage Table 7. Association Between CD3 T Cells and Survival Unadjusted and Adjusted for BWH Disease Stage HR (95% CI); P HR (95% CI); P Unadjusted Adjusted Unadjusted Adjusted All 1.03 ( ); ( );.10 Epithelial 1.01 ( ); ( );.80 Nonepithelial 1.10 ( ); ( );.005 Abbreviations: 95% CI, 95% confidence interval; BWH, Brigham and Women s Hospital; HR, hazard ratio. All 2.02 ( ); ( );.37 Epithelial 1.19 ( ); ( );.63 Nonepithelial 3.98 ( ); ( );.05 Abbreviations: 95% CI, 95% confidence interval; HR, hazard ratio. patients with MPM, Hegmans et al demonstrated that the MPM leukocyte infiltrate is rich in macrophages. 10 Furthermore, a body of evidence has recently emerged that supports a symbiotic relation between tumor cells and TAM. These data suggest that tumors attract TAM and, reciprocally, TAM sustain the survival of tumors via a variety of mechanisms including promotion of angiogenesis and metastases. In many human cancers including those of the lung, breast, cervix, bladder, ovary, and pancreas, the presence of extensive TAM infiltrates has been shown to correlate with poor prognosis. 19,30-33 In other tumors, including those of the brain and prostate, there is conflicting evidence regarding the role of macrophages in survival outcomes. 19 To our knowledge, the relation between tumor-infiltrating macrophages and clinical outcomes in patients with MPM is unknown. Immune dysregulation occurs in patients with cancer. Tumor-derived factors affect immune reactions not only locally within the tumor but also peripherally in the bone marrow. This results in abnormal myelopoiesis and the accumulation of potentially immunosuppressive circulating and tumor-infiltrating myelomonocytic cells. Leukocytosis, for example, has been shown to be a negative predictor of survival for many cancers, including mesothelioma, 34,35 and may result from unregulated production of tumor-derived hematopoietic cytokines. High levels of macrophage inflammatory protein and monocyte chemotactic protein-1 are found in the pleural effusions of patients with MPM. 10 In addition, strikingly high amounts of the immunosuppressive cytokine transforming growth factor (TGF)-b and the proangiogenic cytokine vascular endothelial growth factor (VEGF) are found in these effusions, 36 both of which induce chemotaxis of monocytes through monocyte expression of the high-affinity TGF-b receptor 37 and the VEGF receptor. 38 Monocytes are central cells of the innate immune system that constitute approximately 10% of the human circulating peripheral leukocyte pool. Their scavenging and bactericidal properties consign them to a pivotal role in innate immune surveillance. Their involvement in tumor progression is incompletely understood but high preoperative blood monocyte counts have been shown to be correlatedwithworseoverallsurvivalinseveralhumantumors including gastric, colorectal, and renal carcinoma; melanoma; and head and neck carcinoma Monocytosis has been shown to predict tumor recurrence in patients with hepatocellular carcinoma 11 and is associated with tumors of greater size and higher grade in soft tissue sarcoma. 39 In the current study, we demonstrated that preoperative monocytosis is associated with worse overall survival in patients with Cancer November 15,
9 both epithelial and nonepithelial MPM. Although monocyte counts may be influenced by chemotherapy, we did not find a relation between monocyte counts and preoperative chemotherapy in the 9.3% of patients receiving this treatment. Similarly, the preoperative monocyte count retained its predictive value in survival when adjusted for preoperative chemotherapy (data not shown). One of the most important functions of monocytes is to serve as a systemic reservoir of myeloid precursors for the renewal of tissue macrophages. 40 Macrophages are specialized phagocytic cells that have highly heterogeneous functions depending on their tissue localization and polarization state. Schematically dichotomizing macrophage function, macrophages can be considered to be polarized into M1 ( classically activated ) or M2 ( alternatively activated ) states. In general, M1 macrophages are regarded as soldiers, defending the host from microbial infections and malignancy, producing high amounts of inflammatory cytokines, and activating productive immune responses. M2 macrophages are involved in tissue remodeling, the production of immunoregulatory cytokines such as IL-10, and blunting of immune reactions. The majority of TAM exhibit characteristics of M2 polarization such as expression of M2-associated genes including CD163, the production of anti-inflammatory cytokines, and immunosuppressive function. 41 The tumor microenvironment likely influences the polarization states of macrophages and, in vitro, human MPM cell lines induce human monocyte cell lines to develop functional properties of M2 macrophages. 42 We have found that macrophages within MPM tumors possess a cell surface phenotype in line with an M2, or immunoregulatory, cell type with high expression of the scavenger receptors CD163 and CD206, both of which have been associated with an alternatively activated phenotype of macrophages in humans, 31,43 and high expression of IL-4Ra. Intumor-bearing mice,il-4ra helps to define a population of myeloid-derived suppressor cells (MDSC) that are present in the blood and spleens of tumor-bearing mice and possess immunosuppressive functions. 44 In human tumors, the role of IL-4Ra is not well defined; however, in patients with colon cancer or melanoma, this molecule was recently found to be up-regulated on fractions of circulating mononuclear and polymorphonuclear cells that were suppressors of T-cell function. 45 To our knowledge, this is the first report of high expression of IL-4Ra in human tumor-infiltrating macrophages. The mechanisms by which circulating and tumorinfiltrating myeloid cells in MPM may contribute to tumor progression were not examined in the current study. In patients with stage IV melanoma, monocyte-derived IL-10 was found to be an independent predictor of survival, 46 and in patients with metastatic renal cell cancer, monocytosis was associated with decreased PBMC cytotoxic activity. 14 In mice, MDSC suppress the functional antitumor activities of CD4 and CD8 T cells via the production of nitric oxide and arginase, and through the induction of regulatory T cells. 47 In patients with renal cell cancer, a circulating pool of arginase-expressing CD11b þ CD15 þ CD14 - MDSC-like cells was described that blunted T cell proliferation and interferon-c production. 48 In the tumor microenvironment, TAM release a wide repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor cell proliferation, angiogenesis, invasion, and metastasis. 49 Although the majority of these mechanisms have been elucidated in murine systems, freshly isolated human TAM have been shown to suppress tumor antigen-specific T cell function 22 and produce high levels of IL MPM is a devastating cancer with limited effective treatment options. The nonepithelial histologic variant of MPM is particularly aggressive and patients with this pathology have an even worse prognosis compared with those with the epithelial variant, 3 functionally separating epithelial and nonepithelial MPM into 2 distinct tumor types with different biologic behavior. The results of the current study suggest that the immune response to MPM may differ between patients with epithelial and nonepithelial tumors. Patients with nonepithelial MPM were found to have a higher number of circulating monocytes and although there was no difference with regard to the number of tumor-infiltrating macrophages in these 2 groups, there was a striking difference in their prognostic value, with a high density of tumor-infiltrating macrophages signifying markedly decreased overall survival in the nonepithelial histology group. Although the reason for this is not clear, we surmise that the cytokine milieu and immune cell networks within the tumor microenvironment differ between these 2 pathologic variants of MPM in a way that favors the protumor function of macrophages infiltrating nonepithelial MPM. It is interesting to note that we have also demonstrated a correlation with decreased overall survival and a high CD3 T cell infiltrate in patients with nonepithelial, but not those with epithelial, MPM. The reason for this is uncertain. Because it has been shown that a high CD8 T cell infiltrate is associated with a survival advantage in patients with MPM, 9 we surmise that the association between increased tumor Cancer November 15, 2011
H. Richard Alexander, Jr., M.D. Department of Surgery and The Greenebaum Cancer Center University of Maryland School of Medicine Baltimore, Md
Major Advances in Cancer Prevention, Diagnosis and Treatment~ Why Mesothelioma Leads the Way H. Richard Alexander, Jr., M.D. Department of Surgery and The Greenebaum Cancer Center University of Maryland
More informationMesothelioma. Malignant Pleural Mesothelioma
Mesothelioma William G. Richards, PhD Brigham and Women s Hospital Malignant Pleural Mesothelioma 2,000-3,000 cases per year (USA) Increasing incidence Asbestos (50-80%, decreasing) 30-40 year latency
More informationClinical Indications and Results Following Chest Wall Resection
Clinical Indications and Results Following Chest Wall Resection for Recurrent Malignant Pleural Mesothelioma Ali SO, Burt BM, Groth SS, DaSilva MC, Yeap BY, Richards WG, Baldini EH and Sugarbaker DJ. Division
More informationOncos Therapeutics: ONCOS THERAPEUTICS Personalized Cancer Immunotherapy. March 2015. Antti Vuolanto, COO and co-founder
Oncos Therapeutics: Personalized Cancer Immunotherapy ONCOS THERAPEUTICS Personalized Cancer Immunotherapy March 2015 Antti Vuolanto, COO and co-founder 1 History of Oncos Therapeutics 2002 2007 2009 Research
More informationUpdate on Mesothelioma
November 8, 2012 Update on Mesothelioma Intro incidence and nomenclature Update on Classification Diagnostic specimens Morphologic features Epithelioid Histology Biphasic Histology Immunohistochemical
More informationCharacteristics of Malignant Pleural Mesothelioma in Women
Characteristics of Malignant Pleural Mesothelioma in Women Andrea S. Wolf, MD, MPH, William G. Richards, PhD, Tamara R. Tilleman, MD, PhD, Lucian Chirieac, MD, Shelley Hurwitz, PhD, Raphael Bueno, MD,
More informationExtrapleural Pneumonectomy for Malignant Mesothelioma: Pro. Joon H. Lee 9/17/2012
Extrapleural Pneumonectomy for Malignant Mesothelioma: Pro Joon H. Lee 9/17/2012 Malignant Pleural Mesothelioma (Epidemiology) Incidence: 7/mil (Japan) to 40/mil (Australia) Attributed secondary to asbestos
More informationبسم هللا الرحمن الرحيم
بسم هللا الرحمن الرحيم Updates in Mesothelioma By Samieh Amer, MD Professor of Cardiothoracic Surgery Faculty of Medicine, Cairo University History Wagner and his colleagues (1960) 33 cases of mesothelioma
More informationScreening, early referral and treatment for asbestos related cancer
Screening, early referral and treatment for asbestos related cancer Marc de Perrot, MD, MSc, FRCSC Toronto Mesothelioma Research Program University of Toronto Asbestos related diseases Mesothelioma Lung
More informationMesothelioma. 1. Introduction. 1.1 General Information and Aetiology
Mesothelioma 1. Introduction 1.1 General Information and Aetiology Mesotheliomas are tumours that arise from the mesothelial cells of the pleura, peritoneum, pericardium or tunica vaginalis [1]. Most are
More informationIndependent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens
Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens Assunta De Rienzo, Ph.D. 1, Robert W. Cook, Ph.D. 2,
More informationObjectives. Mylene T. Truong, MD. Malignant Pleural Mesothelioma Background
Imaging of Pleural Tumors Mylene T. Truong, MD Imaging of Pleural Tumours Mylene T. Truong, M. D. University of Texas M.D. Anderson Cancer Center, Houston, TX Objectives To review tumors involving the
More informationBrigham and Women s Hospital, Boston, MA, USA; 2 Verastem, Inc., Boston, MA, USA
Determination of Biomarker Response in a Phase II Window of Opportunity Study of Defactinib (VS 6063), a Focal Adhesion Kinase (FAK) Inhibitor, in Patients with Resectable Malignant Pleural Mesothelioma
More informationTargeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma
The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.
More informationPost-operative intrapleural chemotherapy for mesothelioma
Post-operative intrapleural chemotherapy for mesothelioma Robert Kratzke, MD John Skoglund Chair for Lung Cancer Research Section of Heme-Onc-Transplant University of Minnesota Medical School Efficacy
More informationReport series: General cancer information
Fighting cancer with information Report series: General cancer information Eastern Cancer Registration and Information Centre ECRIC report series: General cancer information Cancer is a general term for
More informationL Lang-Lazdunski, A Bille, S Marshall, R Lal, D Landau, J Spicer
Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine and systemic chemotherapy in malignant pleural mesothelioma. A 10-year experience. L Lang-Lazdunski, A Bille, S Marshall, R Lal,
More informationAccelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma
Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma Marc de Perrot, Ronald Feld, Natasha B Leighl, Andrew Hope, Thomas K Waddell, Shaf Keshavjee,
More informationMalignant Mesothelioma Current Approaches to a Difficult Problem. Raja M Flores, MD Thoracic Surgery Memorial Sloan-Kettering Cancer Center
Malignant Mesothelioma Current Approaches to a Difficult Problem Raja M Flores, MD Thoracic Surgery Memorial Sloan-Kettering Cancer Center Malignant Pleural Mesothelioma Clinical Presentation Insidious
More informationResearch Article Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma
Disease Markers Volume 2015, Article ID 282145, 5 pages http://dx.doi.org/10.1155/2015/282145 Research Article Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma Emanuela Taioli,
More informationSINPE trial, Ann Surg 2009. Overall morbidity. Minor Major. Infectious Non infectious. Post-hoc analysis WL < %5 (n=379) WL between 5-10% (n=49)
Chinese International Symposium on Nutritional Oncology Changchun, June 20-21 2014 IMMUNONUTRITION IN CANCER PATIENTS IMMUNONUTRITION IN SURGERY OBJECTIVE To get the patient undergoing major surgery for
More informationCancer Immunotherapy: Can Your Immune System Cure Cancer? Steve Emerson, MD, PhD Herbert Irving Comprehensive Cancer Center
Cancer Immunotherapy: Can Your Immune System Cure Cancer? Steve Emerson, MD, PhD Herbert Irving Comprehensive Cancer Center Bodnar s Law Simple Things are Important Very Simple Things are Very Important
More informationAdvances in Treatment of Malignant Pleural Mesothelioma: A Reason for Hope
Advances in Treatment of Malignant Pleural Mesothelioma: A Reason for Hope Daniel H. Sterman, M.D. Associate Professor of Medicine and Surgery Co-Director, PENN Mesothelioma and Pleural Program University
More informationMalignant Mesothelioma: an Update
Malignant Mesothelioma: an Update Nico van Zandwijk Asbestos Diseases Research Institute Bernie Banton Centre University of Sydney Australia Physicians Week RACP 19-5-2009 Health Risks of Asbestos Fibers
More informationEffects of Herceptin on circulating tumor cells in HER2 positive early breast cancer
Effects of Herceptin on circulating tumor cells in HER2 positive early breast cancer J.-L. Zhang, Q. Yao, J.-H. Chen,Y. Wang, H. Wang, Q. Fan, R. Ling, J. Yi and L. Wang Xijing Hospital Vascular Endocrine
More informationTargeted Therapy What the Surgeon Needs to Know
Targeted Therapy What the Surgeon Needs to Know AATS Focus in Thoracic Surgery 2014 David R. Jones, M.D. Professor & Chief, Thoracic Surgery Memorial Sloan Kettering Cancer Center I have no disclosures
More informationCancer and the immune system: can we beat cancer at its own game?
Cancer and the immune system: can we beat cancer at its own game? Andrew R. Haas, MD, PhD Assistant Professor of Medicine University of Pennsylvania Medical Center Philadelphia, Pa Why can t immune
More informationThe Value of Thyroid Transcription Factor-1 in Cytologic Preparations as a Marker for Metastatic Adenocarcinoma of Lung Origin
Anatomic Pathology / TTF-1 IN CYTOLOGY OF BODY FLUIDS The Value of Thyroid Transcription Factor-1 in Cytologic Preparations as a Marker for Metastatic Adenocarcinoma of Lung Origin Jonathan L. Hecht, MD,
More informationUpdate on Clinical Trials and Foundation Funded Grants
Update on Clinical Trials and Foundation Funded Grants Mary Hesdorffer, MS, APRN-BC Medical Liaison Meso Foundation www.curemeso.org Delivering the Diagnosis Delivering the Diagnosis Day 1 Taking control
More informationAnalysis of the colorectal tumor microenvironment using integrative bioinformatic tools
MLECNIK Bernhard & BINDEA Gabriela Analysis of the colorectal tumor microenvironment using integrative bioinformatic tools INSERM U872, Jérôme Galon Team15: Integrative Cancer Immunology Cordeliers Research
More informationLuis D. Carcorze Soto, MD PGY-3
Luis D. Carcorze Soto, MD PGY-3 Peritoneal Surface Malignancies Peritoneum Patient Selection Operative Technique HIPEC EPIC Primary: Primary Peritoneal Carcinoma Malignant Peritoneal Mesothelioma Metastatic:
More informationImmuno-Oncology Therapies to Treat Lung Cancer
Immuno-Oncology Therapies to Treat Lung Cancer What you need to know ONCHQ14NP07519 Introduction: Immuno-oncology represents an innovative approach to cancer research that seeks to harness the body s own
More informationMalignant Mesothelioma State of the Art
Malignant Mesothelioma State of the Art Paul Baas The Netherlands Cancer Institute August 12, 2011, Carlsbad, CA Summary Diagnosis; epithelial type subdivided Pleiomorphic vs other Staging: IASLC-IMIG
More informationMesoPDT. Photodynamic Therapy for malignant pleural mesothelioma ONCO-THAI. Image Assisted Laser Therapy for Oncology
MesoPDT Photodynamic Therapy for malignant pleural mesothelioma ONCO-THAI Image Assisted Laser Therapy for Oncology Unité Inserm ONCO-THAI «Image Assisted Laser Therapy for Oncology» Inserm ONCO-THAI "Image
More informationspecific B cells Humoral immunity lymphocytes antibodies B cells bone marrow Cell-mediated immunity: T cells antibodies proteins
Adaptive Immunity Chapter 17: Adaptive (specific) Immunity Bio 139 Dr. Amy Rogers Host defenses that are specific to a particular infectious agent Can be innate or genetic for humans as a group: most microbes
More informationPathophysiology of bone metastasis : how does it apply to pain treatment in palliative care? JP Vuillez, Grenoble, France
Pathophysiology of bone metastasis : how does it apply to pain treatment in palliative care? JP Vuillez, Grenoble, France Bone metastases 70 % of prostate and breast cancers 30 % of lung, bladder and thyroid
More informationB Cells and Antibodies
B Cells and Antibodies Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School Lecture outline Functions of antibodies B cell activation; the role of helper T cells in antibody production
More informationLung Cancer: More than meets the eye
Lung Cancer Education Program November 23, 2013 Lung Cancer: More than meets the eye Shantanu Banerji MD, FRCPC Presenter Disclosure Faculty: Shantanu Banerji Relationships with commercial interests: Grants/Research
More informationClinical cases in Malignant Pleural Mesothelioma: Adherence to the ESMO Clinical Practice Guidelines
Clinical cases in Malignant Pleural Mesothelioma: Adherence to the ESMO Clinical Practice Guidelines Wieneke Buikhuisen The Netherlands Cancer Institute Amsterdam The Netherlands Case (1) Male, 56 year
More informationA Genetic Analysis of Rheumatoid Arthritis
A Genetic Analysis of Rheumatoid Arthritis Introduction to Rheumatoid Arthritis: Classification and Diagnosis Rheumatoid arthritis is a chronic inflammatory disorder that affects mainly synovial joints.
More informationCD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy
CD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy Joseph M. Tuscano, Jason Kato, David Pearson, Chengyi Xiong, Laura Newell, Yunpeng Ma, David R. Gandara,
More informationEnhancing Anti-Tumor Activity of Checkpoint Inhibition
Enhancing Anti-Tumor Activity of Checkpoint Inhibition Jeffrey Schlom, Ph.D. Laboratory of Tumor Immunology and Biology (LTIB) Center for Cancer Research National Cancer Institute, NIH Laboratory of Tumor
More informationThis presentation may contain forward-looking statements, which reflect Trillium's current expectation regarding future events. These forward-looking
Q1/2016 This presentation may contain forward-looking statements, which reflect Trillium's current expectation regarding future events. These forward-looking statements involve risks and uncertainties
More informationPredictive Biomarkers for PD1 Pathway Inhibitor Immunotherapy
Predictive Biomarkers for PD1 Pathway Inhibitor Immunotherapy Michael B. Atkins, M.D. Deputy Director Georgetown-Lombardi Comprehensive Cancer Center Michael Atkins, MD Consulting Fees (e.g., advisory
More informationAdditional file 1. Progress of phase II clinical trials of Panagen
Additional file 1. Progress of phase II clinical trials of Panagen Documentation Phase II clinical trial of preparation Panagen was performed in compliance with the following documentation: Approval of
More informationWhat is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function:
Cancer is a genetic disease: Inherited cancer Sporadic cancer What is Cancer? Cancer typically involves a change in gene expression/function: Qualitative change Quantitative change Any cancer causing genetic
More informationA disease and antibody biology approach to antibody drug discovery
A disease and antibody biology approach to antibody drug discovery Björn Frendéus, PhD VP, Preclinical research Presenter: Björn Frendéus Date: 2011-11-08 1 Antibodies have revolutionized Cancer Treatment!
More informationHow To Treat Mesothelioma With A Tumor Stem Cell Inhibitor
FAK INHIBITOR DEFACTINIB (VS-6063) TARGETS MESOTHELIOMA CANCER STEM CELLS Rationale for maintenance therapy after conventional therapy Jonathan Pachter, Ph.D. Vice President of Research, Verastem, Inc.
More informationMalignant Pleural Mesothelioma in Singapore
RESEARCH COMMUNICATION C SP Yip 1, HN Koong 2, CM Loo 3, KW Fong 1* Abstract Aim: To examine the clinical characteristics and outcomes of malignant pleural mesothelioma (MPM) in Singapore. Methods and
More information1 page Overview. CONCURRENT 1D, 1E, 1F Biology & Pathogenesis Multi-Modality Immunology 1
1 page Overview 21 Oct Tuesday 1500 on REGISTRATION 1800 Welcome Reception & Cocktails at the Cape Town International Conference Centre (CTICC) 22 Oct Wednesday 0730 REGISTRATION 0830 OPENING 0900 PLENARY
More information10 th EADO Congress Vilnius, 7-10 May 2014. Ipilimumab update. Michele Maio
10 th EADO Congress Vilnius, 7-10 May 2014 Ipilimumab update Michele Maio Medical Oncology and Immunotherapy, Department of Oncology University Hospital of Siena, Istituto Toscano Tumori SIENA, ITALY Evolving
More informationmicrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved
microrna 2 micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved Regulate gene expression by binding complementary regions at 3 regions of target mrnas Act as negative
More informationCorporate Medical Policy
Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: adoptive_immunotherapy 11/1993 3/2016 3/2017 3/2016 Description of Procedure or Service The spontaneous regression
More informationHistorical Basis for Concern
Androgens After : Are We Ready? Mohit Khera, MD, MBA Assistant Professor of Urology Division of Male Reproductive Medicine and Surgery Scott Department of Urology Baylor College of Medicine Historical
More informationSMALL CELL LUNG CANCER
Protocol for Planning and Treatment The process to be followed in the management of: SMALL CELL LUNG CANCER Patient information given at each stage following agreed information pathway 1. DIAGNOSIS New
More informationMALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY
MALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY Sisko Anttila, MD, PhD Jorvi Hospital Laboratory of Pathology Helsinki University Hospital Espoo, Finland 2nd Nordic Conference on Applied
More informationSummary of treatment benefits
Risk Management Plan PEMETREXED Powder for concentrate for Solution for infusion Pemetrexed is also indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non small cell
More informationNew strategies in anticancer therapy
癌 症 診 療 指 引 簡 介 及 臨 床 應 用 New strategies in anticancer therapy 中 山 醫 學 大 學 附 設 醫 院 腫 瘤 內 科 蔡 明 宏 醫 師 2014/3/29 Anti-Cancer Therapy Surgical Treatment Radiotherapy Chemotherapy Target Therapy Supportive
More informationELISA BIO 110 Lab 1. Immunity and Disease
ELISA BIO 110 Lab 1 Immunity and Disease Introduction The principal role of the mammalian immune response is to contain infectious disease agents. This response is mediated by several cellular and molecular
More informationDendritic Cells: A Basic Review *last updated May 2003
*last updated May 2003 Prepared by: Eric Wieder, PhD MD Anderson Cancer Center Houston, TX USA What is a dendritic cell? Dendritic cells are antigen-presenting cells (APCs) which play a critical role in
More informationIdentification of CD4+ T cell epitopes specific for the breast cancer associated antigen NY-BR-1
9/8/2015 Identification of CD4+ T cell epitopes specific for the breast cancer associated antigen NY-BR-1 Stefan Eichmüller, PhD GMP & T Cell Therapy Unit, German Cancer Research Center, Heidelberg, Germany
More informationMalignant pleural mesothelioma P/D vs. EPP
3 rd International Thoracic Oncology Congress Dresden, September 13 15, 2012 Malignant pleural mesothelioma P/D vs. EPP Walter Weder, MD Professor of Surgery Dokumentenname Datum Seite 1 Extrapleural Pneumonectomy
More informationASBESTOS EXPOSURE AND SARCOMATOID MALIGNANT PLEURAL MESOTHELIOMA Gorantla Sambasivarao 1, Namballa Usharani 2, Tupakula Suresh Babu 3
ASBESTOS EXPOSURE AND SARCOMATOID MALIGNANT PLEURAL MESOTHELIOMA Gorantla Sambasivarao 1, Namballa Usharani 2, Tupakula Suresh Babu 3 HOW TO CITE THIS ARTICLE: Gorantla Sambasivarao, Namballa Usharani,
More informationThe immune system. Bone marrow. Thymus. Spleen. Bone marrow. NK cell. B-cell. T-cell. Basophil Neutrophil. Eosinophil. Myeloid progenitor
The immune system Basophil Neutrophil Bone marrow Eosinophil Myeloid progenitor Dendritic cell Pluripotent Stem cell Lymphoid progenitor Platelets Bone marrow Thymus NK cell T-cell B-cell Spleen Cancer
More informationRecommendations for the Reporting of Pleural Mesothelioma
Recommendations for the Reporting of Pleural Mesothelioma Association of Directors of Anatomic and Surgical Pathology * DOI: 10.1309/6A30YQHBMTHEJTEM It has been evident for decades that pathology reports
More informationNCCN Non-Small Cell Lung Cancer V.1.2011 Update Meeting 07/09/10
Guideline Page and Request NSCL-3 Stage IA, margins positive delete the recommendation for chemoradiation. Stage IB, IIA, margins positive delete the recommendation for chemoradiation + Stage IIA, Stage
More informationMALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY
MALIGNANT MESOTHELIOMA CLASSIFICATION MALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY Sisko Anttila, MD, PhD Jorvi Hospital Laboratory of Pathology Helsinki University Hospital Espoo,
More informationDetection and staging of recurrent prostate cancer is still one of the important clinical problems in prostate cancer. A rise in PSA or biochemical
Summary. 111 Detection and staging of recurrent prostate cancer is still one of the important clinical problems in prostate cancer. A rise in PSA or biochemical recurrence (BCR) is the first sign of recurrent
More informationA912: Kidney, Renal cell carcinoma
A912: Kidney, Renal cell carcinoma General facts of kidney cancer Renal cell carcinoma, a form of kidney cancer that involves cancerous changes in the cells of the renal tubule, is the most common type
More informationTemporal Trends in Demographics and Overall Survival of Non Small-Cell Lung Cancer Patients at Moffitt Cancer Center From 1986 to 2008
Special Report Temporal Trends in Demographics and Overall Survival of Non Small-Cell Lung Cancer Patients at Moffitt Cancer Center From 1986 to 2008 Matthew B. Schabath, PhD, Zachary J. Thompson, PhD,
More informationA new score predicting the survival of patients with spinal cord compression from myeloma
A new score predicting the survival of patients with spinal cord compression from myeloma (1) Sarah Douglas, Department of Radiation Oncology, University of Lubeck, Germany; sarah_douglas@gmx.de (2) Steven
More informationPredictive Biomarkers for Tumor Immunotherapy: Are we ready for clinical implementation? Howard L. Kaufman Rush University
Predictive Biomarkers for Tumor Immunotherapy: Are we ready for clinical implementation? Howard L. Kaufman Rush University Changing Paradigms in Cancer Treatment Potential Uses of Biomarkers Adverse event
More informationOutline. Workup for metastatic breast cancer. Metastatic breast cancer
Metastatic breast cancer Immunostain Update: Diagnosis of metastatic breast carcinoma, emphasizing distinction from GYN primary 1/3 of breast cancer patients will show metastasis 1 st presentation or 20-30
More informationMesothelioma: Questions and Answers
CANCER FACTS N a t i o n a l C a n c e r I n s t i t u t e N a t i o n a l I n s t i t u t e s o f H e a l t h D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s Mesothelioma: Questions
More informationMalignant pleural mesothelioma: outcome of limited surgical management
Interactive Cardiovascular and Thoracic Surgery 2 (2003) 30 34 Institutional review Thoracic general Malignant pleural mesothelioma: outcome of limited surgical management Peter G. Phillips a, George Asimakopoulos
More informationPROTOCOL OF THE RITA DATA QUALITY STUDY
PROTOCOL OF THE RITA DATA QUALITY STUDY INTRODUCTION The RITA project is aimed at estimating the burden of rare malignant tumours in Italy using the population based cancer registries (CRs) data. One of
More informationGeneral Rules SEER Summary Stage 2000. Objectives. What is Staging? 5/8/2014
General Rules SEER Summary Stage 2000 Linda Mulvihill Public Health Advisor NCRA Annual Meeting May 2014 National Center for Chronic Disease Prevention and Health Promotion Division of Cancer Prevention
More informationPost-recurrence survival in completely resected stage I non-small cell lung cancer with local recurrence
Post- survival in completely resected stage I non-small cell lung cancer with local J-J Hung, 1,2,3 W-H Hsu, 3 C-C Hsieh, 3 B-S Huang, 3 M-H Huang, 3 J-S Liu, 2 Y-C Wu 3 See Editorial, p 185 c A supplementary
More informationUses of Flow Cytometry
Uses of Flow Cytometry 1. Multicolour analysis... 2 2. Cell Cycle and Proliferation... 3 a. Analysis of Cellular DNA Content... 4 b. Cell Proliferation Assays... 5 3. Immunology... 6 4. Apoptosis... 7
More informationTumour Markers. What are Tumour Markers? How Are Tumour Markers Used?
Dr. Anthony C.H. YING What are? Tumour markers are substances that can be found in the body when cancer is present. They are usually found in the blood or urine. They can be products of cancer cells or
More informationTreatment of mesothelioma in Bloemfontein, South Africa
European Journal of Cardio-thoracic Surgery 24 (2003) 434 440 www.elsevier.com/locate/ejcts Treatment of mesothelioma in Bloemfontein, South Africa W.J. de Vries*, M.A. Long Cardiothoracic Department,
More informationIntroduction. About 10,500 new cases of acute myelogenous leukemia are diagnosed each
Introduction 1.1 Introduction: About 10,500 new cases of acute myelogenous leukemia are diagnosed each year in the United States (Hope et al., 2003). Acute myelogenous leukemia has several names, including
More informationPET/CT in Lung Cancer
PET/CT in Lung Cancer Rodolfo Núñez Miller, M.D. Nuclear Medicine and Diagnostic Imaging Section Division of Human Health International Atomic Energy Agency Vienna, Austria GLOBOCAN 2012 #1 #3 FDG-PET/CT
More informationAn Introduction To Immunotherapy And The Promise Of Tissue Phenomics
An Introduction To Immunotherapy And The Promise Of Tissue Phenomics INSIDE: n The Potential of Immunotherapy n Towards an Understanding of Immunotherapy n Current Approaches to Immunotherapy n The Immunotherapy
More informationInternational Beryllium Conference, Montreal, Canada March 10, 2005
Alternative Lymphocyte Proliferation Tests: BrdU and Flow Cytometry Based Tests International Beryllium Conference, Montreal, Canada March 10, 2005 Tim K. Takaro Department of Environmental and Occupational
More informationAvastin: Glossary of key terms
Avastin: Glossary of key terms Adenocarcinoma Adenoma Adjuvant therapy Angiogenesis Anti-angiogenics Antibody Antigen Avastin (bevacizumab) Benign A form of carcinoma that originates in glandular tissue.
More informationMULTIPLE MYELOMA. Dr Malkit S Riyat. MBChB, FRCPath(UK) Consultant Haematologist
MULTIPLE MYELOMA Dr Malkit S Riyat MBChB, FRCPath(UK) Consultant Haematologist Multiple myeloma is an incurable malignancy that arises from postgerminal centre, somatically hypermutated B cells.
More informationSmall Cell Lung Cancer
Small Cell Lung Cancer Types of Lung Cancer Non-small cell carcinoma (NSCC) (87%) Adenocarcinoma (38%) Squamous cell (20%) Large cell (5%) Small cell carcinoma (13%) Small cell lung cancer is virtually
More informationGUIDELINES FOR THE MANAGEMENT OF LUNG CANCER
GUIDELINES FOR THE MANAGEMENT OF LUNG CANCER BY Ali Shamseddine, MD (Coordinator); as04@aub.edu.lb Fady Geara, MD Bassem Shabb, MD Ghassan Jamaleddine, MD CLINICAL PRACTICE GUIDELINES FOR THE TREATMENT
More information7. Prostate cancer in PSA relapse
7. Prostate cancer in PSA relapse A patient with prostate cancer in PSA relapse is one who, having received a primary treatment with intent to cure, has a raised PSA (prostate-specific antigen) level defined
More informationLEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials
LEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials OUR FOCUS ABOUT emerging treatments Presentation for: Judith E. Karp, MD Advancements for Acute Myelogenous Leukemia Supported by an unrestricted educational
More informationLYMPHOMA. BACHIR ALOBEID, M.D. HEMATOPATHOLOGY DIVISION PATHOLOGY DEPARTMENT Columbia University/ College of Physicians & Surgeons
LYMPHOMA BACHIR ALOBEID, M.D. HEMATOPATHOLOGY DIVISION PATHOLOGY DEPARTMENT Columbia University/ College of Physicians & Surgeons Normal development of lymphocytes Lymphocyte proliferation and differentiation:
More informationThe Ontario Cancer Registry moves to the 21 st Century
The Ontario Cancer Registry moves to the 21 st Century Rebuilding the OCR Public Health Ontario Grand Rounds Oct. 14, 2014 Diane Nishri, MSc Mary Jane King, MPH, CTR Outline 1. What is the Ontario Cancer
More informationINTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER Prospective Mesothelioma Staging Project
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER Prospective Mesothelioma Staging Project Data Forms and Fields in CRAB Electronic Data Capture System - Reduced Set - Pivotal data elements for developing
More informationMESOTHELIOMA. Not Just a Late Night Commercial. Graciela Hoal, RN, MSN, ACNP-BC
MESOTHELIOMA Not Just a Late Night Commercial Graciela Hoal, RN, MSN, ACNP-BC Saturday Session Thoracic Surgery Nurse Practitioner Greater Los Angeles Veteran Affairs Objectives Course Objectives: Discuss
More informationImmune Checkpoint Blockade in Acute Myeloid Leukemia. Kinsey McCormick Hematology Fellow s Conference January 10, 2014
Immune Checkpoint Blockade in Acute Myeloid Leukemia Kinsey McCormick Hematology Fellow s Conference January 10, 2014 Overview Overview of immune checkpoints Immune checkpoints as mechanism of immune evasion
More informationThe Most Common Autoimmune Disease: Rheumatoid Arthritis. Bonita S. Libman, M.D.
The Most Common Autoimmune Disease: Rheumatoid Arthritis Bonita S. Libman, M.D. Disclosures Two googled comics The Normal Immune System Network of cells and proteins that work together Goal: protect against
More informationNEW CLINICAL RESEARCH OPTIONS IN PANCREATIC CANCER IMMUNOTHERAPY. Alan Melcher Professor of Clinical Oncology and Biotherapy Leeds
NEW CLINICAL RESEARCH OPTIONS IN PANCREATIC CANCER IMMUNOTHERAPY Alan Melcher Professor of Clinical Oncology and Biotherapy Leeds CANCER IMMUNOTHERAPY - Breakthrough of the Year in Science magazine 2013.
More informationTitle: Mapping T cell epitopes in PCV2 capsid protein - NPB #08-159. Date Submitted: 12-11-09
Title: Mapping T cell epitopes in PCV2 capsid protein - NPB #08-159 Investigator: Institution: Carol Wyatt Kansas State University Date Submitted: 12-11-09 Industry summary: Effective circovirus vaccines
More informationA new score predicting the survival of patients with spinal cord compression from myeloma
A new score predicting the survival of patients with spinal cord compression from myeloma (1) Sarah Douglas, Department of Radiation Oncology, University of Lubeck, Germany; sarah_douglas@gmx.de (2) Steven
More information