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

J Clin Invest. 2024 Sep 3;134(17):e183675. doi: 10.1172/JCI183675.

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.

MeSH terms

  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / immunology
  • Endometrial Neoplasms* / pathology
  • Endometrial Neoplasms* / therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy
  • Intra-Abdominal Fat* / immunology
  • Obesity / immunology
  • Obesity / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human