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

SUMMARY

Although obesity is a major risk factor for cancer, it may also improve the response to cancer therapy. Prof. Bourquin’s team investigated the impact of obesity on the efficacy of immune checkpoint inhibitors (ICI). In male mice, they found that obesity promoted tumour growth but enhanced the response to ICI. This improvement was associated with higher expression of immune-related genes within the tumour and increased infiltration of tumour-specific CD8+ T cells.

The team further observed that obesity in mice was linked to higher estrogen levels and enrichment of estrogen response genes in the tumour. The efficacy of anti–programmed cell death 1 (anti–PD-1) therapy was reduced when the aromatase inhibitor letrozole, which blocks estrogen production, was administered. Mechanistically, they showed that adipocyte-derived estrogens increased antigen presentation by dendritic cells and boosted tumour-specific CD8+ T cell cytotoxicity.

Finally, Prof. Bourquin’s team reported that overweight and obese men with melanoma responded better to ICI, with higher estrogen levels correlating with improved response and survival. These results suggest that estrogens may serve as a predictive factor of response to ICI in men with melanoma.

Full article:  https://doi.org/10.1172/jci.insight.189758

WHY IS IT IMPORTANT?

Immunotherapy has revolutionized melanoma care, but many patients do not respond to this treatment. Surprisingly, obesity, which is usually considered to be a risk factor for cancer, may actually help improve outcomes in men. In this study, obese male mice with melanoma responded better to anti-PD-1 immunotherapy, and this was linked to higher levels of estrogens produced by fat tissue. These estrogens boosted the activity of dendritic cells and killer T cells, helping the immune system to attack tumours. Notably, overweight and obese men with melanoma also exhibited improved survival rates when their estrogen levels were higher. These findings suggest that estrogen levels could help predict which patients are most likely to benefit from immunotherapy.

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