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Unhealthy visceral fat is associated with improved efficacy of immunotherapy in endometrial cancer
Matthew L. Steinhauser
Matthew L. Steinhauser
Published September 3, 2024
Citation Information: J Clin Invest. 2024;134(17):e183675. https://doi.org/10.1172/JCI183675.
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Commentary

Unhealthy visceral fat is associated with improved efficacy of immunotherapy in endometrial cancer

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Abstract

Obesity is a known driver of endometrial cancer. In this issue of the JCI, Gómez-Banoy and colleagues investigated a cohort of patients with advanced endometrial cancer treated with immune checkpoint inhibitors targeting the interaction between programmed cell death receptor-1 (PD-1) and its ligand (PD-L1). Notably, a BMI in the overweight or obese range was paradoxically associated with improved progression-free and overall survival. A second paradox emerged from CT analyses of visceral adipose tissue, viewed as an unhealthy fat depot in most other contexts, the quantity of which was also associated with improved treatment outcomes. Though visceral adiposity may have value as a biomarker to inform personalized treatment strategies, of even greater impact would be if a therapeutic strategy emerges from the future identification of adipose-derived mediators of this putative anticancer immune-priming effect.

Authors

Matthew L. Steinhauser

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Figure 1

VAT may prime antitumor immunity in women with endometrial cancer and obesity.

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VAT may prime antitumor immunity in women with endometrial cancer and ob...
Three potential mechanisms explain the paradox underlying the relationship between putative unhealthy VAT and positive clinical responses to immunotherapy in endometrial cancer with abdominal obesity. VAT is a known contributor to a generalized state of chronic sterile metabolic inflammation, in part through systemic release of various inflammatory signals. There may also be a more specific signal emanating from VAT that acts distantly on specific immune cell types in the tumor. Finally, VAT is replete with immune cells and therefore is a theoretical reservoir supporting immune cell trafficking to the tumor site.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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