AUTHOR=Hao Jiatao , Li Meng , Zhang Taohong , Yu Hui , Liu Ying , Xue Yan , An Ruifang , Wang Shuai
TITLE=Prognostic Value of Tumor-Infiltrating Lymphocytes Differs Depending on Lymphocyte Subsets in Esophageal Squamous Cell Carcinoma: An Updated Meta-Analysis
JOURNAL=Frontiers in Oncology
VOLUME=10
YEAR=2020
URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00614
DOI=10.3389/fonc.2020.00614
ISSN=2234-943X
ABSTRACT=Background: Tumor-infiltrating lymphocytes (TILs) play a role in the anti-tumor immune response, and are often found in esophageal squamous cell carcinoma (ESCC).
Methods: We performed a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes of TILs based on their abundance and infiltrating location. A literature search of PubMed/Medline, Embase, Web of Science and the Cochrane Library was conducted. Studies that investigated the prognostic significance of generalized, CD8+, CD4+, FoxP3+, CD3+, and CD45O+ TILs in ESCC patients were included.
Results: In pooled analysis, generalized TILs infiltrating the entire tumor mass were positively associated with disease-free survival (DFS), with a univariate-related hazard ratio (HR) of 0.630 [95% confidence interval (CI) 0.415–0.955], and also positively associated with overall survival (OS), with a univariate-related HR of 0.586 (0.447–0.770) and a multivariate-related HR of 0.621 (0.439–0.878). The pan-tumor, intra-tumor and peri-tumor CD8+ TILs had a favorable effect on OS, with univariate-related HRs of 0.733 (0.555–0.968), 0.797 (0.660–0.962), and 0.776 (0.635–0.948), respectively. Similar results were observed in CD8+ TILs that infiltrated the whole tumor mass, with a multivariate-related HR of 0.705 (0.524–0.947). CD4+, FoxP3+, CD3+, and CD45O+ TILs were not linked to DFS or OS. Subtypes and spatial locations of TILs seemed to influence study outcomes.
Conclusions: Experimental and analytical methods of future studies should be carefully designed to avoid overestimating the effect of TILs on prognosis. Our meta-analysis confirms the prognostic efficacy of generalized TILs and CD8+ TILs in esophageal squamous cell carcinoma (ESCC) patients.