The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma (original) (raw)
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Oncogen, 2019
Background: Ovarian cancer is a malignancy with a complex immune suppressive microenvironment mediated by the recruitment or induction of cluster differentiation factor 4+ (CD4+) regulatory T cells. The purpose of this study was to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIc/IV of High-Grade Serous Ovarian Carcinoma (HGSC), and its relationship to treatment response. Patients and Methods: We retrospectively identified 33 patients diagnosed with HGSC and treated with neoadjuvant platinum-paclitaxel from 2005-2014. Pre-and post-neoadjuvant treatment tissue samples were submitted to immunohistochemical analyses with anti-CD3, CD4 and CD8 antibodies for the identification of tumor-infiltrating lymphocytes (TILs). The staining results were analyzed and were blindly evaluated with respect to clinical features. Pathological response classification to NACT was made according to Steffen Bohm. Results: The mean age of patients was 63.44 years (46.53-84.14). Germline BRCA1/2-mutation status was negative in 58.82% of patients (10/17); BRCA1/2-mutation was positive in 11.76 %(2/17); and a variant of uncertain significance was found in 29.41 %(5/17). The majority of patients (78.8%) were stage IIIc. The area under the ROC curve of post-surgery TILs for complete pathological response was: CD4 (epithelial):
Biomarkers in Medicine, 2019
Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic i...
Prognostic Effect of Epithelial and Stromal Lymphocyte Infiltration in Non-Small Cell Lung Cancer
Clinical Cancer Research, 2008
The major value of prognostic markers in potentially curable non-small cell lung cancer (NSCLC) should be to guide therapy after surgical resection. In this regard, the patients' immune status at the time of resection may be important and also measurable. The immune system has paradoxical roles during cancer development. However, the prognostic significance of tumorinfiltrating lymphocytes is controversial.The aim of this study is to elucidate the prognostic significance of epithelial and stromal lymphocyte infiltration in NSCLC. Experimental Design: Tissue microarrays from 335 resected NSCLC, stage I to IIIA were constructed from duplicate cores of viable and representative neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the epithelial and stromal CD4 + , CD8 + , and CD20 + lymphocytes. Results: In univariate analyses, increasing numbers of epithelial CD8 + (P = 0.023), stromal CD8 + (P = 0.002), epithelial CD20 + (P = 0.023), stromal CD20 + (P < 0.001), and stromal CD4 + (P < 0.001) lymphocytes correlated significantly with an improved disease-specific survival. No such relation was noted for epithelial CD4 + cells. Furthermore, a low level of stromal CD8 + lymphocyte infiltration was associated with an increased incidence of angiolymphatic invasion (P = 0.032). In multivariate analyses, a high number of stromal CD8 + (P = 0.043) and CD4 + (P = 0.002) cells were independent positive prognostic factors for disease-specific survival. Conclusions: High densities of CD4 + and CD8 + lymphocytes in the stroma are independent positive prognostic indicators for resected NSCLC patients. This may suggest that these cells are mediating a strong antitumor immune response in NSCLC.
Immunologic character of tumor infiltrating lymphocytes in ovarian carcinoma
Chinese Journal of Cancer Research, 2000
Objective: To study immunologic character of tumor-infiltrating lymphocytes (TIL) on post in vitro expansion in ovarian carcinoma, and evaluate the prospects by adopting TIL treatment of ovarian carcinoma at an advanced stage. Methods: Cellular phenotype changes in TIL were analyzed by flow cytometry. By means of molecular biology and immunologic methods, ability to secrete cytokines and anti-tumor activities of in TIL was studied. Results: Difference of cellular phenotypes in TIL was probably related to the type, feature and resource of the tumor. TIL obtained from phoroplast and parenchyma was dominant in CD3÷CD4 ÷. TIL obtained from tumor tissues, around microvessels and ascitic fluid was dominant in CD3÷CD8 ÷. Concentration of rlL-2 in vitro played a significant role in immunologic character of TIL. By means of rIL-2 expansion in vitro, TIL has apparently been improved in competence of secreting some cytokines, such as IL-2, TNF-Ct, IFN-y, and antitumor activities.The activated TIL was more stimulated by further adding anti-CD3 or PHA (suitable concentration), which significantly increased its ability to secrete cytokines. Treatment with TIL+CTX or TIL+ rIL-2, could apparently improve phenotypes in peripheral blood of patients, with definitive effects. Conclusion: Immunologic activities of TIL in vitro are apparently improved by rIL2 expansion. Regression of
Advances in anatomic pathology, 2017
Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL ass...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2000
Tumor-infiltrating lymphocytes, apoptosis, and angiogenesis have a pivotal role in tumor growth control. This study was undertaken to analyze the associations of these factors and their role in the prognosis, defined as survival time, of 56 patients operated on for small cell lung carcinoma (SCLC). Immunohistochemically detected T cells and macrophages were the most abundant tumor-infiltrating lymphocytes in SCLC, whereas the number of B cells was small. There was a trend in the number of intratumoral cytotoxic/suppressor CD8 cells that were associated with the extent of apoptotic bodies in SCLC, as measured by in situ 3'-end labeling of apoptotic DNA. A high number of intratumoral T cells and CD8 cells were associated significantly with a low tumor size (<3 cm) and low tumor stage (stages I-II). A high number of intratumoral macrophages were associated with a low tumor stage and angiogenesis, as measured by microvessel density. A high number of T cells, CD8 cells, and macrop...
British Journal of Cancer
Tumour-infiltrating lymphocytes (TILs) are often found in tumours, presumably reflecting an immune response against the tumour. We carried out a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes based on the presence of TILs in cancer. A Pubmed and Embase literature search was designed. Studies were included, in which the prognostic significance of intratumoural CD3+, CD4+, CD8+, and FoxP3+ lymphocytes, as well as ratios between these subsets, were determined in solid tumours. In pooled analysis, CD3+ TILs had a positive effect on survival with a hazard ratio (HR) of 0.58 (95% confidence interval (CI) 0.43-0.78) for death, as did CD8+ TILs with a HR of 0.71 (95% CI 0.62-0.82). FoxP3+ regulatory TILs were not linked to overall survival, with a HR of 1.19 (95% CI 0.84-1.67). The CD8/FoxP3 ratio produced a more impressive HR (risk of death: HR 0.48, 95% CI 0.34-0.68), but was used in relatively few studies. Sample size and follow-up time se...