T-cell activation is associated with high-grade serous ovarian cancer survival.

Abstract

High-grade serous ovarian cancer (HGSOC) is an aggressive disease that is largely resistant to today's immunotherapies. Here, we aimed to investigate the prognostic significance of CTLA4, PD-1, and T-cell activation status in HGSOC. Using a publicly accessed microarray dataset including 260 HGSOC samples, we calculated Kaplan-Meier survival curves for overall survival (OS), evaluated associations with multivariate Cox regression models to evaluate the associations, and summarized using a hazard ratio (HR). The correlations between PD-1 gene expression and that of other genes were calculated by Pearson correlation. Multivariate survival analyses showed that high PD-1 expression but not CTLA4 was associated with longer OS (HR=0.69; 95% confidence interval [CI]=0.52-0.91; p=0.01), and that higher T-cell activation score was associated with better outcome (HR=0.74; 95% confidence interval [CI]=0.58-0.95; p=0.02). The top three PD-1 highly correlated genes were SIRPG (r=0.90, p < 2E-16), FASL (r=0.89, p < 2E-16), and CD8a (r=0.87, p < 2E-16). HGSOC patients' OS is positively associated T-cell activation score and PD-1 expression but not CTLA4. T cell activation score may serve as a candidate for personalized immunotherapy in HGSOC. The application of anti-PD-1 therapy to HGSOC should be cautious.