Title:Concomitant Expression of Inhibitory Molecules for T cell Activation Predicts Poor Survival in Patients with Esophageal Squamous Cell Carcinoma
Volume: 21
Issue: 3
Author(s): Zhijun Chen, Kexin Cao, Jinghang Zhang, Zhuangzhuang Liu, Liaoxun Lu, Bo Qi, Lijin Shi, Rong Huang* Song Zhao*
Affiliation:
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang,China
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou,China
Keywords:
ESCC, T cells, PD-1, TIM-3, BTLA, survival.
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 the 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, co-inhibitory molecules regulating T cell
activation are poorly documented.
Objective: We aim to evaluate how the presence of inhibitory check-point molecules in T cells
could impact the survival of patients.
Methods: We performed a 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 the
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 the 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.