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

TLDR

Tumor‑infiltrating T cells have been documented in ovarian carcinoma, but their association with clinical outcome remains unclear. This study examined 186 advanced‑stage ovarian carcinoma specimens to determine whether intratumoral T‑cell presence correlates with clinical outcomes. The authors used immunohistochemistry on frozen tumor sections and real‑time PCR to identify CD3+ intratumoral T cells in 102 of 186 advanced‑stage ovarian carcinomas. Patients whose tumors contained intratumoral T cells had markedly better progression‑free and overall survival, with five‑year overall survival rates of 38% versus 4.5% overall and 73.9% versus 11.9% among complete responders, and intratumoral T‑cell presence independently predicted delayed recurrence or death while correlating with higher IFN‑γ, IL‑2, and chemokine expression and lower VEGF levels.

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.