Estrogens determine the efficacy of cancer immunotherapy in obese males with melanoma.

ABSTRACT: Although obesity is a major risk factor for cancer, it may also improve the response to cancer therapy. Here we investigated the impact of obesity on the efficacy of immune checkpoint inhibitors (ICI). In male mice, obesity promoted tumor growth but enhanced the response to ICI. This was associated with higher expression of immune-related genes within the tumor and enhanced infiltration of tumor-specific CD8+ T cells. Further, obesity in mice was associated with higher estrogen levels and enrichment of estrogen response genes in the tumor, and anti-programmed cell death 1 (anti-PD-1) efficacy was reduced upon administration of the aromatase inhibitor letrozole, which blocks the production of estrogens. Mechanistically, adipocyte-derived estrogens increased antigen presentation by dendritic

SUBMITTER: Dupuychaffray E 

PROVIDER: S-EPMC12288961 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature