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Tumor-Infiltrating CD4+ Lymphocytes Predict a Favorable Survival in Patients with Operable Esophageal Squamous Cell Carcinoma

Kaiyan Chen, Ziyu Zhu, Nan Zhang, Guoping Cheng, Fanrong Zhang, Jiaoyue Jin, Junzhou Wu, Lisha Ying, Weimin Mao, Dan Su

Cancer Research Institute, Zhejiang Cancer Hospital and Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province, Hangzhou, Zhejiang, China (mainland)

Med Sci Monit 2017; 23:4619-4632

DOI: 10.12659/MSM.904154

Available online:

Published: 2017-09-26

BACKGROUND: The immune status within the tumor microenvironment has not been well determined in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the distributions of tumor-infiltrating T lymphocytes (TILs), and analyze their associations with clinical characteristics and prognosis; as well as investigate the expression of programmed death-ligand 1 (PD-L1) which has been identified as a favorable indicator of prognosis in our previous study on ESCC.
MATERIAL AND METHODS: Five hundred and thirty-six patients who underwent radical surgery for ESCC between January 2008 and April 2012 in Department of Thoracic Surgery at Zhejiang Cancer Hospital were included in the study. Immunohistochemistry was used to investigate the infiltration of various TILs (CD3+, CD4+, CD8+ T lymphocytes) in ESCC tissues. Chi-square test and Cox proportional hazards regression were used to explore the correlations between TILs abundance and clinicopathological variables and survival.
RESULTS: The infiltration of intraepithelial CD4+ (iCD4+) lymphocytes was markedly higher than it in the stromal region (44.2% for intraepithelial versus 28.9% for stromal, p<0.001). Moreover, increased iCD4+ lymphocytes were significantly associated with longer overall survival (OS, p=0.001) in univariate analysis and were identified as an independent predictor for improved OS in multivariate analysis (hazard ratio [HR]=0.67, 95% confidence interval [CI]: 0.51–0.88, p=0.040). Neither the infiltration of CD3+ nor CD8+ lymphocytes showed the prognostic value in ESCC (p>0.05). Unexpectedly, combined with our previous study results, the TILs infiltration in ESCC showed an inverse association with the expression of PD-L1 (p=0.027).
CONCLUSIONS: Our results suggested that iCD4+ lymphocytes infiltration could be a favorable indicator for prognosis in ESCC.

Keywords: Antigens, CD4, Esophageal Neoplasms, Immunochemistry, Survival Analysis, T-Lymphocytes, Helper-Inducer