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

Arghavan Alisoltani1, Xinru Qiu2, Lukasz Jaroszewski2

  • 1Division of Biomedical Sciences, University of California Riverside School of Medicine, Riverside, CA, USA; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

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Smoking impacts cancer immunity differently in men and women. This study reveals gender-specific immune cell changes in smokers, particularly increased plasma cells in women, impacting immunotherapy strategies.

Keywords:
Immune cell typesSingle-cell RNA-seqTobacco smokingTumor microenvironment

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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.