Prognostic value of tumor-infiltrating lymphocytes in esophageal cancer: an updated meta-analysis of 30 studies with 5,122 patients

Background: The prognostic role of tumor-infiltrating lymphocytes (TILs) in esophageal cancer (EC) patients is controversial; therefore, we performed a meta-analysis to obtain a consensus. Methods: The PubMed, PubMed Central, Embase, Cochrane Library, and Web of Science databases were searched. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed effect or random effect models depending on the heterogeneity. Results: A total of 30 articles comprising 5,122 patients were included in this meta-analysis. High levels of generalized TIL infiltration were associated with better overall survival (OS) (HR = 0.67, 95% CI: 0.47-0.95, P=0.02) in EC patients. High CD8+ T-cell infiltration and high CD4+ T-cell infiltration were associated with better OS (HR =0.68, 95% CI: 0.60-0.78, P<0.001; HR =0.70, 95% CI: 0.57-0.85, P<0.001, respectively). However, the pooled results showed that neither CD3+ nor FOXP3+ T-cell infiltration were associated with patient survival (P>0.05). Moreover, for esophageal squamous cell carcinoma (ESCC), high CD8+ T lymphocyte infiltration in the TN ( Tumor nest) or TS ( Tumor stroma) significantly predicted better OS (pooled HR =0.70, 95% CI: 0.57-0.85; P=0.001; pooled HR =0.77, 95% CI: 0.65-0.91; P=0.003). Conclusions: High levels of generalized TILs, high CD8+ T-cell infiltration and high CD4+ T-cell infiltration have the potential to serve as prognostic markers in EC patients. Moreover, high CD8+ TIL in TNs or TS can predict better OS in ESCC patients.