Prognostic value of immune cells in the tumor microenvironment of early-stage lung cancer: A meta-analysis

Background: Early-stage non-small cell lung cancer (NSCLC) patients carry significant risk of recurrence post-surgery. In-depth characterization of the immune tumor microenvironment (TME) can have prognostic value. This study aimed to evaluate the association of individual immune cell types in the TME with clinical outcomes in surgically resected, early-stage NSCLC. Methods: We performed a systematic literature search of the National Library of Medicine database through November 2019, investigating predefined biomarkers (CD3+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD20+ B cells, CD56+ & CD57+ Natural Killer (NK) cells, CD68+ Tissue Associated Macrophages (TAMS), FoxP3+ T regulatory cells, and Mast Cells (MC)), and their association with survival following PRISMA guidelines. Results: Studies that adjusted for important clinical covariates (such as stage and age) showed that higher levels of CD8+ cytotoxic T cells were associated with improved OS (HR = 0.68; 95% CI, 0.50-0.93) and DFS (HR = 0.60; 95% CI, 0.41-0.87), while increased CD20+ B cells (HR = 0.16; 95% CI, 0.04-0.64) and CD 56/57+ NK cells (HR = 0.50; 95% CI, 0.26-0.95) were associated with improved OS; lung cancers with increased FoxP3+ T regulatory cells (HR = 2.22; 95% CI, 1.47-3.34) had worse OS. Conclusions: Immune cell components of the TME have prognostic value in early-stage, surgically resected NSCLC, and may reveal which patients are more likely to need additional systemic treatment, including immunotherapy. Clinical covariates need to be considered when evaluating the prognostic value of immune cells in the TME.