Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia 19104, USA.
New England Journal of Medicine (Impact Factor: 55.87). 01/2003; 348(3):203-13. DOI: 10.1056/NEJMoa020177
Source: PubMed


Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established.
We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction.
CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor.
The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.

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Available from: Stephen C Rubin, Oct 22, 2015
    • "surgery and current chemotherapeutic regimens are rather ineffective , novel treatment options are of paramount importance (Patel, 2011). Tumour cells are often surrounded by infiltrating inflammatory cells, particularly lymphocytes and macrophages (Smyth et al, 2006) and there is compelling evidence that tumour-infiltrating T-lymphocytes have a favourable effect on patient survival in several malignant tumours, including colorectal (Galon et al, 2006; Mlecnik et al, 2011), ovarian (Zhang et al, 2003), breast (Mahmoud et al, 2011) and pancreatic (Fukunaga et al, 2004) cancer. By investigating a large cohort of BTC, we were able to show a favourable prognostic effect of tumour-infiltrating T-lymphocytes in ECC and GBAC, but not in ICC (Goeppert et al, 2013). "
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    ABSTRACT: Background: Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC. Methods: MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival. Results: BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4(+) and CD8(+)) and macrophages. Conclusions: Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis.British Journal of Cancer advance online publication, 13 October 2015; doi:10.1038/bjc.2015.337
    British Journal of Cancer 10/2015; DOI:10.1038/bjc.2015.337 · 4.84 Impact Factor
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    • "This failure may partially be attributed to most studies being directed towards the tumour cell-intrinsic events and ignoring the contributory effects of variation in the local immune response. The role of the tumour microenvironment in the survival of tumour cells, and the dual roles of cancer immunoediting via tumour-promoting inflammation and suppression, is becoming well recognised (Zhang et al, 2003; Galon et al, 2006; Schreiber et al, 2011; Baxevanis et al, 2013). There is also increasing awareness that pre-existing adaptive immune status affect response to subsequent therapy across various cancers. "
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    British Journal of Cancer 03/2015; DOI:10.1038/bjc.2015.81 · 4.84 Impact Factor
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    • "Cells of the immune system Function Reference CD3+ T lymphocytes The presence of infiltrating lymphocytes is associated with a higher rate Zhang et al., 2003 [25] of survival in patients diagnosed with ovarian cancer Stage III and IV compared with those patients who did not have such lymphocytes; the presence of these lymphocytes is related to a better prognosis of the clinical response ovarian cancer. T CD3+ CD8+ The presence of these lymphocytes is related to a better prognosis for the Helal et al., 2004 [26] lymphocytes clinical response of ovarian cancer. "
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    ABSTRACT: The objective of study was review studies that have investigated the immune response in the presence of a malignant ovarian neoplasia. A review of the literature was performed to identify studies of malignant ovarian neoplasia, particularly studies that addressed the potential for cytokines, nitric oxide, and lymphocytes to mediate an immune response against ovarian cancer. Certain subsets of tumor-infiltrating leukocytes and/or tumor-associated leukocytes have been found to correlate with an improved disease prognosis, while other lymphocyte subsets (such as CD3+/CD4+/CD25+ T cells) have been associated with a poor diagnosis. These data suggest that cytokines can have a protective role, or can promote an immune system defense against a cancer. In particular, certain cytokines (e.g., IL 8, IL 10) represent attractive candidates for the development of new diagnostic, prognostic, and therapeutic strategies for the treatment of ovarian cancer. Keywords: Cytokines, nitric oxide, malignant ovarian neoplasia, cluster of differentiation, lymphocytes.
    European journal of gynaecological oncology 11/2014; 35(5):487-491. DOI:10.12892/ejgot24622014 · 0.61 Impact Factor
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