Article

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: 54.42). 01/2003; 348(3):203-13. DOI: 10.1056/NEJMoa020177
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
137 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although described for the first time some decades ago, the contribution of the immune system to the establishment of tumors has not been extensively pursued for a long time. Over the last decade, however, more and more evidence has been accumulating concerning the role the immune system plays in tumor development and progression and its possible role in patient prognosis. In addition, interest is growing in preclinical and clinical research concerning the use of the immune system in the treatment of cancer. Immunotherapy for gynecological cancers in general, and for endometrial cancer in particular, is still in its infancy. Only a small number of studies, with varying success rates, have been published. Here, we provide a concise overview of the literature available on the role of the immune system in the normal endometrium and in endometrial cancer, in addition to the possible implications for future immunotherapeutic studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of Reproductive Immunology 01/2015; DOI:10.1016/j.jri.2014.12.006 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aim: Tumor infiltrating lymphocytes (TILs) have been a subject of growing scientific interest; however, a full picture of their role in cancer pathogenesis is still unclear. This study aimed to reveal correlations between TIL grade and clinicopathological features, especially 5-year survival parameters in cutaneous malignant melanoma (CMM) patients. Materials and Methods: Presence of TILs was assessed in hematoxylin and eosin staining by using routine diagnostic histopathological specimens form 104 patients with cutaneous melanoma. Results: In the entire group of 104 patients, decreasing TIL intensity was a highly negative prognostic factor and indicated considerably shorter overall survival (OS), cancer specific overall survival (CSOS) and disease-free survival (DFS). We also report a significant association between decreased TIL intensity and worse prognosis in lymph node negative patients. Shorter survival (p=0.002 for OS, p=0.038 for CSOS and p=0.011 for DFS) was observed in patients with negative sentinel lymph node biopsy (SLNB), as well as in patients with lack of metastases in regional lymph nodes (p=0.034 for OS, p<0.001 for CSOS and DFS). Conclusion: Our results indicate that TIL grade is a valuable diagnostic parameter that may be helpful in risk stratification in CMM.
    Anticancer research 01/2015; 35(1):351-358. · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical outcomes, such as recurrence-free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathological network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies.
    Cancer and metastasis reviews 12/2014; DOI:10.1007/s10555-014-9540-2 · 6.45 Impact Factor