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Concomitant Expression of Inhibitory Molecules for T cell Activation Predicts Poor Survival in Patients with Esophageal Squamous Cell Carcinoma

[ Vol. 21 , Issue. 3 ]

Author(s):

Zhijun Chen, Kexin Cao, Jinghang Zhang, Zhuangzhuang Liu, Liaoxun Lu, Bo Qi, Lijin Shi, Rong Huang* and Song Zhao*Pages 244-253 (10)

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.

Keywords:

ESCC, T cells, PD-1, TIM-3, BTLA, survival.

Affiliation:

Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou

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