Immune microenvironment composition in non-small cell lung cancer and its association with survival.

ABSTRACT

OBJECTIVES: In non-small cell lung cancer (NSCLC), the immune system and possibly its composition affect survival. In this in silico study, the immune infiltrate composition in NSCLC patients was evaluated. METHODS: Gene expression data of tumors from early NSCLC patients were obtained from Gene Expression Omnibus (GEO). With CIBERSORT, 22 immune cell fractions were estimated. RESULTS: The immune infiltrate of 1430 pretreatment NSCLC patients contained mostly plasma cells, macrophages and CD8 T cells. Higher fractions of resting mast and CD4 T-helper cells were associated with longer overall survival (OS) (HR = 0.95, P < 0.01; HR = 0.98, = 0.04, respectively) and higher fractions of M2 macrophages and active dendritic cells with shorter survival (HR = 1.02, P = 0.03; HR = 1.03, P = 0.05, respectively). Adenocarcinoma patients with survival data (n = 587) showed higher fractions of resting mast and resting CD4 T cells, and lower M0 macrophages than squamous cell carcinoma (n = 254), which were associated with OS (HR = 0.95, P = 0.04; HR = 0.97, P = 0.01; HR = 1.03, P = 0.01, respectively). Fractions of memory B cells, naïve CD4 T cells and neutrophils had different associations with survival depending on the subtype. Smokers had had higher fractions of regulatory T cell, follicular helper T cell, neutrophil and M2 macrophage, which were associated with shorter survival (HR = 1.3, P < 0.01; HR = 1.13, P = 0.02; HR = 1.09, P = 0.03; HR = 1.04, P = 0.02, respectively). CONCLUSION: Pretreatment differences in immune cell composition in NSCLC are associated with survival and depend on smoking status and histological subtype. Smokers' immune composition is associated with lower survival.