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      CD247 expression is associated with differentiation and classification in ovarian cancer

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          Abstract

          Ovarian cancer (OC) is one of the most common malignant tumors in female reproductive system and most OC cases are diagnosed at an advanced stage with the overall 5-year survival rate below 40%. The function of CD247 enhances T-cell antigen receptor (TCR) signaling cascade and it is necessary for assembling of the TCR/CD3 complex on the surface of T lymphocytes. It is well established that defective CD247 function leads to impaired activation of T cells upon engagement of the TCR.

          Flow cytometry was used to examine the difference of CD247 + T lymphocyte between the OC and ovarian cyst, immunohistochemistry analysis was used to investigate the correlation between CD247 expression and clinicopathologic features of epithelial OC patients.

          Our study showed that the expression of CD247 in peripheral blood lymphocytes from patients with OC is decreased compared with ovarian cyst patients and the expression of CD247 in tumor infiltrating lymphocytes with cancer tissue is decreased compared with adjacent tissues. We showed that abnormal expression of CD247 was related with differentiation and classification in OC.

          Our findings suggested that CD247-targeted treatment could be used as a potential therapeutic strategy for OC.

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          Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis.

          Wei-Ting Hwang, Sarah Adams, Emin Tahirovic … (2012)
          The presence of T cells within the epithelial component of tumors, as histologic evidence of anti-tumor immunity, has been associated with a survival advantage in multiple studies across diverse patient cohorts. We performed a meta-analysis of studies evaluating the prognostic value of tumor-infiltrating lymphocytes (TIL) on survival among women with ovarian cancer and to investigate factors associated with variations in this effect, including patient characteristics, surgical outcomes, tumor histology, and study protocols. Published studies that evaluated the association between TIL and patient survival were identified. Descriptive statistics, outcome data, and study quality were extracted from studies that met inclusion criteria. Hazard ratios and 95% confidence intervals were pooled across studies using the random-effects model. Publication bias was investigated using a funnel plot and heterogeneity was assessed with subgroup analysis and I(2) statistics. Ten suitable studies comprising 1815 patients with ovarian cancer were analyzed. Our results demonstrate that a lack of intraepithelial TILs is significantly associated with a worse survival among patients (pooled HR: 2.24, 95% CI; 1.71-2.91). Variations in the prognostic value of TIL status based on debulking status, scoring method, and geographic regions were identified. Intraepithelial TILs are a robust predictor of outcome in ovarian cancer and define a specific class of patients, whose distinct tumor biology should be taken into account in devising appropriate therapeutic strategies. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma.

            Gulsun Erdag, Jochen Schaefer, Mark Smolkin … (2012)
            Immune cells infiltrating the microenvironment of melanoma metastases may either limit or promote tumor progression, but the characteristics that distinguish these effects are obscure. In this study, we systematically evaluated the composition and organization of immune cells that infiltrated melanoma metastases in human patients. Three histologic patterns of immune cell infiltration were identified, designated immunotypes A, B, and C. Immunotype A was characterized by no immune cell infiltrate. Immunotype B was characterized by infiltration of immune cells limited only to regions proximal to intratumoral blood vessels. Immunotype C was characterized by a diffuse immune cell infiltrate throughout a metastatic tumor. These immunotypes represented 29%, 63%, and 8% of metastases with estimated median survival periods of 15, 23, and 130 months, respectively. Notably, from immunotypes A to C, there were increasing proportions of B cells and decreasing proportions of macrophages. Overall, the predominant immune cells were T cells (53%), B cell lineage cells (33%), and macrophages (13%), with natural killer and mature dendritic cells only rarely present. Whereas higher densities of CD8(+) T cells correlated best with survival, a higher density of CD45(+) leukocytes, T cells, and B cells also correlated with increased survival. Together, our findings reveal striking differences in the immune infiltrate in melanoma metastases in patients, suggesting microenvironmental differences in immune homing receptors and ligands that affect immune cell recruitment. These findings are important, not only by revealing how the immune microenvironment can affect outcomes but also because they reveal characteristics that may help improve individualized therapy for patients with metastatic melanoma.
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              Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity.

              O Nakano, M. Sato, Y Naito … (2001)
              Tumor-infiltrating lymphocytes, particularly CD8(+) T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8(+) but also CD4(+) T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8(+) T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8(+) T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: December 2019
                Publication date (Electronic): 20 December 2019
                Volume: 98
                Issue: 51
                Electronic Location Identifier: e18407
                Affiliations
                [a ]Department of Tumor Biological Treatment
                [b ]Department of Obstetrics and Gynecology
                [c ]Department of pathology, The Third Affiliated Hospital, Soochow University
                [d ]Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, Jiangsu, China.
                Author notes
                [∗ ]Correspondence: Jingting Jiang, Department of Tumor Biological Treatment and Research Center for Cancer Immunotherapy Technology of Jiangsu Province, The Third Affiliated Hospital, Soochow University, Jiangsu, Changzhou 213003, China (e-mail: jiangjingting@ 123456suda.edu.cn ).
                Article
                Publisher ID: MD-D-19-03867 Accession ID: 18407
                DOI: 10.1097/MD.0000000000018407
                PMC ID: 6940041
                PubMed ID: 31861005
                SO-VID: d8928fdf-7deb-4163-a543-341df820f191
                Copyright © Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                Date received : 15 May 2019
                Date revision received : 27 September 2019
                Date accepted : 15 November 2019
                Categories
                Subject: 5600
                Subject: Research Article
                Subject: Quality Improvement Study
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: ovarian cancer,cd247,flow cytometry,immunohistochemistry
                Data availability:
                Keywords: ovarian cancer, cd247, flow cytometry, immunohistochemistry

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