HSF1 Inhibits Antitumor Immune Activity in Breast Cancer by Suppressing CCL5 to Block CD8+ T-cell Recruitment.

ABSTRACT: Heat shock factor 1 (HSF1) is a stress-responsive transcription factor that promotes cancer cell malignancy. To provide a better understanding of the biological processes regulated by HSF1, here we developed an HSF1 activity signature (HAS) and found that it was negatively associated with antitumor immune cells in breast tumors. Knockdown of HSF1 decreased breast tumor size and caused an influx of several antitumor immune cells, most notably CD8+ T cells. Depletion of CD8+ T cells rescued the reduction in growth of HSF1-deficient tumors, suggesting HSF1 prevents CD8+ T-cell influx to avoid immune-mediated tumor killing. HSF1 suppressed expression of CCL5, a chemokine for CD8+ T cells, and upregulation of CCL5 upon HSF1 loss significantly contributed to the recruitment of CD8+ T cells. Thes

SUBMITTER: Jacobs C 

PROVIDER: S-EPMC10790131 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature