Androgen conspires with the CD8⁺ T cell exhaustion program and contributes to sex bias in cancer.

ABSTRACT: Sex bias exists in the development and progression of nonreproductive organ cancers, but the underlying mechanisms are enigmatic. Studies so far have focused largely on sexual dimorphisms in cancer biology and socioeconomic factors. Here, we establish a role for CD8⁺ T cell-dependent antitumor immunity in mediating sex differences in tumor aggressiveness, which is driven by the gonadal androgen but not sex chromosomes. A male bias exists in the frequency of intratumoral antigen-experienced Tcf7/TCF1⁺ progenitor exhausted CD8⁺ T cells that are devoid of effector activity as a consequence of intrinsic androgen receptor (AR) function. Mechanistically, we identify a novel sex-specific regulon in progenitor exhausted CD8⁺ T cells and a pertinen

SUBMITTER: Kwon H 

PROVIDER: S-EPMC9374385 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature