Dyck, Lydia and Prendeville, Hannah and Raverdeau, Mathilde and Wilk, Mieszko M. and Loftus, Roisin M. and Douglas, Aaron and McCormack, Janet and Moran, Bruce and Wilkinson, Michael and Mills, Evanna L. and Doughty, Michael and Fabre, Aurelie and Heneghan, Helen and LeRoux, Carel and Hogan, Andrew E. and Chouchani, Edward T. and O’Shea, Donal and Brennan, Donal and Lynch, Lydia (2022) Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function. Journal of Experimental Medicine, 219 (3). ISSN 0022-1007

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Abstract

Obesity is one of the leading preventable causes of cancer; however, little is known about the effects of obesity on anti-tumor immunity. Here, we investigated the effects of obesity on CD8 T cells in mouse models and patients with endometrial cancer. Our findings revealed that CD8 T cell infiltration is suppressed in obesity, which was associated with a decrease in chemokine production. Tumor-resident CD8 T cells were also functionally suppressed in obese mice, which was associated with a suppression of amino acid metabolism. Similarly, we found that a high BMI negatively correlated with CD8 infiltration in human endometrial cancer and that weight loss was associated with a complete pathological response in six of nine patients. Moreover, immunotherapy using anti-PD-1 led to tumor rejection in lean and obese mice and partially restored CD8 metabolism and anti-tumor immunity. These findings highlight the suppressive effects of obesity on CD8 T cell anti-tumor immunity, which can partially be reversed by weight loss and/or immunotherapy.

Item Type:	Article
Keywords:	Suppressive effects; obese; tumor; microenvironment; CD8 T cell infiltration; effector function;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17748
Identification Number:	https://doi.org/10.1084/jem.20210042
Depositing User:	Andrew Hogan
Date Deposited:	25 Oct 2023 14:28
Journal or Publication Title:	Journal of Experimental Medicine
Publisher:	Rockefeller University Press
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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