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

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. In male mice, obesity promoted tumor growth but enhanced the response to ICI. In contrast, in non-obese mice, no difference in tumor growth was observed between mice receiving anti-PD-1 or isotype control antibodies.Using transcriptome analysis of bulk tumors, we showed a distinct effect of anti-PD-1 treatment in obese versus non-obese mice. We further compared the gene expression profile of tumors from obese and non-obese mice in absence of treatment to investigate the mechanisms behind the increased efficacy of anti-PD-1 in obese mice. Our findings suggest that estrogens could be an obesity-derived factor modulating the sensitivity to PD-1 blockade in male mice.