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

Tobacco smoke is a known carcinogen, mostly due to its genotoxicity, but its effects on the host immune system are also playing an important role. Here, we leveraged recent results on the immune landscape of cancer based on The Cancer Genomic Atlas (TCGA) data analysis and compared the proportions of major classes of tumor-infiltrating immune cells (TIICs) between smokers and never smokers in ten TCGA cancer types. We show that statistically significant changes can be identified in all ten cancers, with increased plasma cell populations and the modified ratio of activated to resting TIICs being the most consistent features distinguishing smokers and never-smokers across different cancers, with both being correlated with survival outcomes. Analysis of existing single-cell RNA-seq data further showed that smoking differentially affects the gene expression profile of cancer patients based on the immune cell type. The smoking-induced changes in the patterns of immune cells and their correlations to survival outcomes are stronger in female smokers.