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Lookup NU author(s): Jing Lim, Grace Mallett, Dr David McDonald, Dr Gill Hulme, Dr Stephanie Laba, Megan Payne, Warren Patterson, Michael Alexander, Dr Jonathan Coxhead, Professor Andrew FilbyORCiD, Professor Ruth Plummer, Professor Penny Lovat, Dr Eugene Healy, Dr Shoba AmarnathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Innate lymphoid cells (ILCs) play a key role in tissue-mediated immunity and can be controlled by coreceptor signaling. Here, we define a subset of ILCs that are Tbet+NK1.1- and are present within the tumor microenvironment (TME). We show programmed death-1 receptor (PD-1) expression on ILCs within TME is found in Tbet+NK1.1- ILCs. PD-1 significantly controlled the proliferation and function of Tbet+NK1.1- ILCs in multiple murine and human tumors. We found tumor-derived lactate enhanced PD-1 expression on Tbet+NK1.1- ILCs within the TME, which resulted in dampened the mammalian target of rapamycin (mTOR) signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1-deficient Tbet+NK1.1- ILCs expressed significantly increased IFNγ and granzyme B and K. Furthermore, PD-1-deficient Tbet+NK1.1- ILCs contributed toward diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate antitumor responses of Tbet+NK1.1- ILCs within the TME.
Author(s): Lim JX, Lai CY, Mallett GE, McDonald D, Hulme G, Laba S, Shapanis A, Payne M, Patterson W, Alexander M, Coxhead J, Filby A, Plummer R, Lovat PE, Sciume G, Healy E, Amarnath S
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Year: 2023
Volume: 120
Issue: 18
Print publication date: 02/05/2023
Online publication date: 25/04/2023
Acceptance date: 07/03/2023
Date deposited: 16/05/2023
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: https://doi.org/10.1073/pnas.2216587120
DOI: 10.1073/pnas.2216587120
PubMed id: 37098069
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