Metabolic reprogramming of terminally exhausted CD8<sup>+</sup> T cells by IL-10 enhances anti-tumor immunity.

Details

Serval ID
serval:BIB_C5D0B4808515
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Metabolic reprogramming of terminally exhausted CD8<sup>+</sup> T cells by IL-10 enhances anti-tumor immunity.
Journal
Nature immunology
Author(s)
Guo Y., Xie Y.Q., Gao M., Zhao Y., Franco F., Wenes M., Siddiqui I., Bevilacqua A., Wang H., Yang H., Feng B., Xie X., Sabatel C.M., Tschumi B., Chaiboonchoe A., Wang Y., Li W., Xiao W., Held W., Romero P., Ho P.C., Tang L.
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Publication state
Published
Issued date
06/2021
Peer-reviewed
Oui
Volume
22
Number
6
Pages
746-756
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
T cell exhaustion presents one of the major hurdles to cancer immunotherapy. Among exhausted CD8 <sup>+</sup> tumor-infiltrating lymphocytes, the terminally exhausted subset contributes directly to tumor cell killing owing to its cytotoxic effector function. However, this subset does not respond to immune checkpoint blockades and is difficult to be reinvigorated with restored proliferative capacity. Here, we show that a half-life-extended interleukin-10-Fc fusion protein directly and potently enhanced expansion and effector function of terminally exhausted CD8 <sup>+</sup> tumor-infiltrating lymphocytes by promoting oxidative phosphorylation, a process that was independent of the progenitor exhausted T cells. Interleukin-10-Fc was a safe and highly efficient metabolic intervention that synergized with adoptive T cell transfer immunotherapy, leading to eradication of established solid tumors and durable cures in the majority of treated mice. These findings show that metabolic reprogramming by upregulating mitochondrial pyruvate carrier-dependent oxidative phosphorylation can revitalize terminally exhausted T cells and enhance the response to cancer immunotherapy.
Pubmed
Web of science
Create date
31/05/2021 8:36
Last modification date
19/06/2021 6:33
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