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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We carried out a systematic review and meta-analysis to evaluate the predictive roles of tumor infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) in breast cancer. A PubMed and Web of Science literature search was designed. Random or fixed effect models were adopted to estimate the summary odds ratio (OR). Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. Publication bias was evaluated using a funnel plot, Egger's test and Begg's test. We included studies where the predictive significance of TILs, and/or TILs subset on the pathologic complete response (pCR) were determined in NAC of breast cancer. A total of 13 published studies (including 3251 patients) were eligible. In pooled analysis, the detection of higher TILs numbers in pre-treatment biopsy was correlated with better pCR to NAC (OR = 3.93, 95% CI, 3.26-4.73). Moreover, TILs predicted higher pCR rates in triple negative (OR = 2.49, 95% CI: 1.61-3.83), HER2 positive (OR = 5.05, 95% CI: 2.86-8.92) breast cancer, but not in estrogen receptor (ER) positive (OR = 6.21, 95%CI: 0.86-45.15) patients. In multivariate analysis, TILs were still an independent marker for high pCR rate (OR = 1.41, 95% CI: 1.19-1.66). For TILs subset, higher levels of CD8+ and FOXP3+ T-lymphocytes in pre-treatment biopsy respectively predicted better pathological response to NAC (OR = 6.44, 95% CI: 2.52-16.46; OR = 2.94, 95% CI: 1.05-8.26). Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80) and multivariate (OR = 0.36, 95% CI: 0.13-0.95) analysis. Higher TILs levels in pre-treatment biopsy indicated higher pCR rates for NAC. TILs subset played different roles in predicting response to NAC.
    PLoS ONE 01/2014; 9(12):e115103. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sarcoid-like reaction is often seen in various types of carcinoma, not only in the primary tumor, but also in regional lymph nodes, and can occur at any time, not only at the time of diagnosis, but also after treatment. However, few cases of hepatopancreatobiliary carcinoma, and no cases of gallbladder cancer with sarcoid-like reaction involving the lymph nodes have been described. This report is the first report of a sarcoid-like reaction involving the lymph nodes in a case of gallbladder cancer. We encountered a rare case of gall bladder cancer with sarcoid-like reaction in the lymph nodes. Since regional lymph node swelling that was difficult to differentiate from metastasis was found preoperatively, swollen nodes were examined histologically using frozen sections. Based on this histology, the swollen nodes were diagnosed as showing sarcoid reaction and therefore extended lymphadenectomy was avoided. The patient did not receive any adjuvant chemotherapy and has shown no recurrence of disease as of 4 years after surgery. Distinguishing between metastasis and sarcoid-like reaction in lymph nodes by preoperative imaging is still difficult. The present case shows that it is important to histologically examine swollen nodes by biopsy or by sampling before deciding on the treatment strategy for gall bladder cancer with swollen lymph nodes.
    BMC Cancer 12/2014; 14(1):946. · 3.32 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