The Expression of Tim-3 in Peripheral Blood of Ovarian Cancer

Abstract

Ovarian cancer remains a challenging disease for which improved treatments are urgently needed. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated the expression of Tim-3 on peripheral CD4+ T and CD8+ T cells in ovarian cancer. A total of 52 ovarian cancer patients and 56 healthy controls were recruited and leukocytes from peripheral blood mononuclear cells were analyzed for Tim-3 surface expression by flow cytometry. Data showed that expression of Tim-3 was significantly increased in both CD4+ and CD8+ T cells in ovarian cancer cases than in controls (p<0.0001 and p<0.0001, respectively). Patients who had recurrent ovarian cancer had a higher proportion of Tim-3+CD4+ T cells than when they were newly diagnosed (p=0.013). When analyzing Tim-3 expression with cancer progression, results revealed elevated Tim-3 expression in both CD4+ and CD8+ T cells in cases with advanced International Federation of Gynecology and Obstetrics (FIGO) staging (III/IV) than those with stage I and II (p=0.009 and p=0.037, respectively). We also tested Tim-3 with tumor grade, and observed that patients with a higher tumor grade (G3) demonstrated further augmented Tim-3 expression in CD4+ and CD8+ T cells compared to those with lower tumor grades (p=0.010 and p=0.042, respectively). Our study suggested that Tim-3 may participate in the development and progression of ovarian cancer by its negative regulation on various T-cell subsets, and Tim-3 expression in CD4+ T cells could serve as a predictive marker for anticancer therapies.