Synapse - Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer

Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer Journal Article

Authors:	Gómez-Banoy, N.; Ortiz, E.; Jiang, C. S.; Dagher, C.; Sevilla, C.; Girshman, J.; Pagano, A.; Plodkowski, A.; Zammarrelli, W. A.; Mueller, J. J.; Aghajanian, C.; Weigelt, B.; Makker, V.; Cohen, P.; Osorio, J. C.
Article Title:	Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer
Abstract:	Background: Obesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association between body mass index (BMI), body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI. Methods: We analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAE) after ICI was also assessed based on BMI status. Results: 524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared to normal BMI patients after treatment with ICI. Multivariable Cox regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/TP53abnormal (CN-H/TP53abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared to normal BMI individuals. Conclusion: Obesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/TP53abn EC molecular subtype. © 2024 American Society for Clinical Investigation. All rights reserved.
Journal Title:	Journal of Clinical Investigation
Volume:	134
Issue:	17
ISSN:	0021-9738
Publisher:	American Society for Clinical Investigation
Date Published:	2024-09-03
Start Page:	e180516
Language:	English
DOI:	10.1172/jci180516
PUBMED:	38900575
PROVIDER:	scopus
PMCID:	PMC11364395
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85196856792&doi=10.1172%2fJCI180516&partnerID=40&md5=1e24b9a61dd44fde05be87efc4bb07fe
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Juan Osorio -- Source: Scopus