Gender differences in smoking-induced changes in the tumor immune microenvironment.

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Smoking is a known carcinogen and affects cancer progression via the immune system.
• Gender influences cancer prevalence and outcomes, but its interaction with smoking's immune effects is unclear.

Purpose of the Study:

• To investigate gender-specific effects of smoking on the tumor immune microenvironment.
• To analyze immune subtypes and cell populations in male and female smokers using large-scale cancer datasets.

Main Methods:

• Analysis of The Cancer Genomic Atlas (TCGA) datasets (n=2724).
• Validation using Expression Project for Oncology (expO) bulk RNA-seq (n=1118) and single-cell RNA-seq (n=14) datasets.
• Comparison of immune subtypes and immune cell abundance between smokers and never-smokers, stratified by gender.

Main Results:

• Female smokers showed altered C1 and C2 immune subtypes, while male smokers had a decreased C6 subtype.
• Gender-specific differences in immune cell populations were observed in smokers across TCGA and expO datasets.
• Increased plasma cell populations were a consistent marker in smokers, especially current female smokers.
• Single-cell data confirmed gender- and immune cell type-specific gene expression changes due to smoking.
• Changes in plasma cell populations correlated more strongly with survival in female smokers.

Conclusions:

• Smoking induces distinct immune microenvironment alterations in female and male cancer patients.
• Plasma cell changes are a key gender-specific smoking-related immune signature.
• Findings support personalized immunotherapy strategies for women smokers based on their unique tumor immune profiles.