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

Sep 27, 2017Medical science monitor : international medical journal of experimental and clinical research

Higher Levels of Certain Immune Cells in Tumors Linked to Better Survival in Operable Esophageal Cancer

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Abstract

Intraepithelial CD4+ lymphocytes were present in 44.2% of esophageal squamous cell carcinoma tissues, significantly higher than the 28.9% found in the stromal region.

Higher levels of intraepithelial CD4+ lymphocytes are significantly associated with longer overall survival in patients with esophageal squamous cell carcinoma.
Increased intraepithelial CD4+ lymphocyte infiltration was identified as an independent predictor for improved overall survival.
No prognostic value was observed for the infiltration of CD3+ or CD8+ lymphocytes in this study.
The infiltration of tumor-infiltrating lymphocytes showed an inverse association with the expression of programmed death-ligand 1 (PD-L1).

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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.

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

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