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

• Published in: Current cancer drug targets Vol. 21; no. 3; p. 244
• Main Authors: Chen, Zhijun, Cao, Kexin, Zhang, Jinghang, Liu, Zhuangzhuang, Lu, Liaoxun, Qi, Bo, Shi, Lijin, Huang, Rong, Zhao, Song
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2021
• Subjects: Adult; Aged; Antigens, CD - metabolism; Biomarkers, Tumor - metabolism; CTLA-4 Antigen - metabolism; Esophageal Neoplasms - immunology; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - immunology; Esophageal Squamous Cell Carcinoma - metabolism; Esophageal Squamous Cell Carcinoma - mortality; Esophageal Squamous Cell Carcinoma - pathology; Female; Follow-Up Studies; Hepatitis A Virus Cellular Receptor 2 - metabolism; Humans; Kaplan-Meier Estimate; Lymphocyte Activation - immunology; Lymphocyte Activation Gene 3 Protein; Male; Middle Aged; Prognosis; Programmed Cell Death 1 Receptor - metabolism; Receptors, Immunologic; Survival Rate; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; BTLA; T cells; TIM-3; PD-1; ESCC; survival
• ISSN: 1873-5576
• DOI: 10.2174/1568009620666201120152333

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