Concomitant expression of inhibitory molecules for T cell activation predicts poor survival in patients with esophageal squamous cell carcinoma

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a major subtype of esophageal cancers. The Five-year survival rate of ESCC is low and molecular targets for ESCC treatment and prognosis assessment are very limited. T cells are critical for clearance of cancer cells and blockade of co-inhibitory molecules for T cell activation has emerged as a promising therapy to treat cancer patients. However, in ESCC patients such co-inhibitory molecules regulating T cell activation is poorly documented.

Objective: We aim to evaluate how the presence of inhibitory check-point molecules in T cells could impact survival of patients.

Methods: We performed follow-up study of 161 patients undergoing resection of esophageal carcinoma from February 2014 to December 2015, by immunohistochemical staining of six co-inhibitory molecules for T cell activation, namely PD-1, CTLA-4, TIM-3, LAG-3, BTLA and A2AR. Expression of each of the six co-inhibitory molecules was analyzed for its correlation with patient survival by Kaplan-Meier survival analysis. We also applied Kaplan-Meier analyses to evaluate concomitant expression of co-inhibitory molecules and their correlation with patient survival.

Results: We found that levels of PD-1, TIM-3 and BTLA can be used as independent prognostic factors for overall survival of patients with ESCC. More importantly, our study found that the co-expression of PD-1 and TIM-3, PD-1 and BTLA, TIM-3 and BTLA significantly reduced the survival of patients with ESCC (P<0.05).

Conclusion: Therefore, our results suggest the necessity of evaluating the tumor tissue expression of co-inhibitory molecules and targeting co-expressed molecules in immunotherapies for ESCC patients.

Keywords: BTLA; ESCC; PD-1; Survival.; T cells; TIM-3.