Prognostic value of the common tumour-infiltrating lymphocyte subtypes for patients with non-small cell lung cancer: A meta-analysis

Background Many previous studies have revealed that tumour-infiltrating lymphocytes (TILs) are significantly associated with prognosis in various tumours. However, this finding remains controversial in non-small cell lung cancer (NSCLC). We performed this meta-analysis systematically to evaluate the prognostic value of TILs in NSCLC. Methods The references were collected by searching the PubMed, EMBASE and Web of Science databases. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized using random or fixed effects models to evaluate the association between TILs and NSCLC survival outcomes. Results A total of 45 interrelated studies were eligible that included 11,448 patients. Pooled analysis showed that a high density of TILs indicated a better overall survival (HR = 0.80, 0.70–0.89) and progression-free survival (HR = 0.73, 0.61–0.85) for patients with NSCLC; a high density of CD3+ TILs in the tumour nest indicated a better overall survival (HR = 0.84, 0.69–0.99) and disease-specific survival (HR = 0.57, 0.34–0.80); a high density of CD4+ TILs in the tumor nest indicated a favourable overall survival (HR = 0.86, 0.76–0.96); a high density of CD8+ TILs indicated a favourable overall survival (HR = 0.995, 0.99–1.0), progression-free survival (HR = 0.52, 0.34–0.71), disease-free survival (HR = 0.64, 0.43–0.85), relapse/recurrence-free survival (HR = 0.42, 0.18–0.67) and disease-specific survival (HR = 0.56, 0.35–0.78); and a high density of CD20+ TILs in the tumour nest indicated a favourable overall survival (HR = 0.65, 0.36–0.94). However, a high density of Foxp3+ TILs in the tumour stroma indicated a worse relapse/recurrence-free survival (HR = 1.90, 1.05–2.76) in NSCLC. Conclusions Our meta-analysis confirmed that high densities of TILs, CD3+TILs, CD4+TILs, CD8+TILs and CD20+TILs in the tumour nest are favourable prognostic biomarkers for patients with NSCLC, and Foxp3+TILs in the tumour stroma are a poor prognostic biomarker.