Large scale analysis of smoking-induced changes in the tumor immune microenvironment

Abstract

Abstract Here, we expanded the recent knowledge on the immune landscape of cancer by performing a comparative analysis of tobacco smoking-induced changes in the populations of major immune cell types between smokers and never-smokers (people who have never smoked). To investigate the immune response of smokers and never-smokers, the relative abundance of immune cell types was calculated by both CIBERSORT and xCell based on TCGA RNA-seq data. We further validated the findings using publicly available bulk RNA-seq and single-cell RNA-seq data from cohorts of cancer patients other than TCGA cohort. We showed statistically significant smoking-induced changes in immune cell populations in all studied cancers. The increase in plasma cell populations and the changes in the ratio of activated to resting immune cell types were the most consistent features distinguishing smokers and never-smokers across different cancers, with both being correlated with survival outcomes. We found that the tobacco-induced changes in populations of immune cells were not as marked in cancers of tissues that are not directly exposed to smoke as in lung cancers and head and neck cancer (LUAD, LUSC, and HNSC). However, the significant differences in survival in several cancer types suggest that even a small shift in the frequency of immune cell types might result in adverse outcomes. We also showed that smoking-induced changes in the patterns of immune cell populations and their correlations to survival outcomes are stronger in female smokers than in males. In general, the findings of this study suggest that certain immune cell types could potentially be used as common prognostic markers and therapeutic targets for active smoker patients.