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

PLoS One. 2020 Nov 10;15(11):e0242173. doi: 10.1371/journal.pone.0242173. eCollection 2020.


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.

Publication types

  • Evaluation Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / standards*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Humans
  • Lung Neoplasms / pathology*
  • Lymphocyte Subsets
  • Lymphocytes, Tumor-Infiltrating / classification*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Predictive Value of Tests
  • Survival Analysis


  • Biomarkers, Tumor

Grant support

Benchao Chen, Gaofeng Li was supported by the National Natural Science Foundation of China [ No.81760554]. Chao Liu was supported by the National Natural Science Foundation of China [ No.81960322] and Joint Program of Applied Basic Research of Yunnan Provincial Department of Science and Technology - Kunming Medical University. [NO.2018FE001(-247)].