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Sex Differences in Colorectal Tumor-Associated T-cell Responses.

Elizabeth Seitz1, Ya-Yu Tsai2, Rebeca Sanz-Pamplona3,4,5,6

  • 1Case Western Reserve University School of Medicine, Cleveland, Ohio.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
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PubMed
Summary

This study found no sex differences in anti-tumor T cell responses in colorectal cancer (CRC). T cell abundance and infiltration improved survival for all patients, regardless of sex.

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Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Colorectal cancer (CRC) exhibits higher incidence and mortality in males compared to females.
  • The biological mechanisms driving these sex-based disparities in CRC remain largely unknown.

Purpose of the Study:

  • To investigate potential sex differences in anti-tumor T cell responses within colorectal cancer.
  • To determine if T cell receptor (TCR) abundance, clonality, and tumor-infiltrating lymphocytes (TILs) differ between sexes.
  • To assess the association between T cell metrics and survival outcomes stratified by sex.

Main Methods:

  • Immunosequencing of tumor samples from two independent cohorts (MECC, N=2,750 and Spanish study, N=444) to analyze T cell receptor (TCR) abundance and clonality.
  • Scoring of tumor-infiltrating lymphocytes per high-powered field (TILs/hpf) in the discovery cohort.
  • Multivariable regression models (logistic and Cox proportional hazards) were used to analyze associations between sex, T cell metrics, and survival, adjusting for prognostic indicators.

Main Results:

  • No significant associations were found between sex and TCR abundance, clonality, or TILs/hpf in either cohort.
  • Increased TCR abundance and TILs/hpf were consistently linked to improved overall and CRC-specific survival across both sexes.
  • No significant interaction was detected between sex and T cell metrics concerning survival outcomes.

Conclusions:

  • Sex differences in colorectal cancer are not explained by variations in the robustness or diversity of tumor-associated T cell responses.
  • The study did not find evidence supporting stronger anti-tumor T cell immunity in females contributing to improved survival.