Prognostic role of tumour-infiltrating lymphocytes assessed by H&E-stained section in gastric cancer: A systematic review and meta-Analysis

Abstract

Objectives Some studies have identified tumour-infiltrating lymphocytes (TILs) in HandE-stained sections of gastric cancer, but the prognostic and clinicopathological significance of this remains unclear. The objective of this study is to evaluate the associations between HandE-based TIL density and prognosis and clinicopathological characteristics of patients with gastric cancer. Design Systematic review and meta-Analysis. Data sources Cochrane Library, PubMed and Embase databases were searched through 25 February 2020. Eligibility criteria Studies evaluating the correlations between TILs assessed by HandE-stained sections and prognosis and clinicopathological characteristics of gastric cancer were included. Data extraction and synthesis Relevant data were extracted and risks of bias were assessed independently by two reviewers. HR and relative risk (RR) with 95% CI were pooled by random-effect models to estimate the associations between TIL density and overall survival (OS) and clinicopathological characteristics, respectively. Results We enrolled nine studies including 2835 cases for the present meta-Analysis. High TILs were associated with superior OS (HR=0.68, 95% CI 0.52 to 0.87, p=0.003) compared with low TILs. High TILs were significantly associated with lower depth of invasion (T3-T4 vs T1-T2) (RR=0.58, 95% CI 0.50 to 0.66, p<0.001), less lymph node involvement (presence vs absence) (RR=0.68, 95% CI 0.56 to 0.81, p<0.001) and earlier TNM (tumour, node, metastasis) stage (III-IV vs I-II) (RR=0.68, 95% CI 0.55 to 0.83, p<0.001). TIL density was not associated with age, gender, Lauren classification or histological grade. The methodology for evaluating TIL and its cut-off value varied across different studies, which might affect the results of our meta-Analysis. Conclusions Our meta-Analysis suggests that HandE-based TIL density is a reliable biomarker to predict the clinical outcomes of patients with gastric cancer. Multicentre, prospective studies are needed to further confirm our findings. PROSPERO registration number CRD42020169877.