JOM KITA KE POLITEKNIK

Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8(+) T Cells (Record no. 778)

MARC details
042 ## - AUTHENTICATION CODE
Authentication code dc
100 10 - MAIN ENTRY--PERSONAL NAME
Personal name Chowdhury, Snehanshu
Relator term author
9 (RLIN) 1183
245 00 - TITLE STATEMENT
Title Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8(+) T Cells
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Name of publisher, distributor, etc. American Association for Cancer Research,
Date of publication, distribution, etc. 2022-07-18.
500 ## - GENERAL NOTE
General note /pmc/articles/PMC7613107/
500 ## - GENERAL NOTE
General note /pubmed/35648389
520 ## - SUMMARY, ETC.
Summary, etc. Effector CD8(+) T cells rely primarily on glucose metabolism to meet their biosynthetic and functional needs. However, nutritional limitations in the tumor microenvironment can cause T-cell hyporesponsiveness. Therefore, T cells must acquire metabolic traits enabling sustained effector function at the tumor site to elicit a robust antitumor immune response. Here, we report that IL12-stimulated CD8(+) T cells have elevated intracellular acetyl CoA levels and can maintain IFNγ levels in nutrient-deprived, tumor-conditioned media (TCM). Pharmacological and metabolic analyses demonstrated an active glucose-citrate-acetyl CoA circuit in IL12-stimulated CD8(+) T cells supporting an intracellular pool of acetyl CoA in an ATP-citrate lyase (ACLY)-dependent manner. Intracellular acetyl CoA levels enhanced histone acetylation, lipid synthesis, and IFNγ production, improving the metabolic and functional fitness of CD8(+) T cells in tumors. Pharmacological inhibition or genetic knockdown of ACLY severely impaired IFNγ production and viability of CD8(+) T cells in nutrient-restricted conditions. Furthermore, CD8(+) T cells cultured in high pyruvate-containing media in vitro acquired critical metabolic features of IL12-stimulated CD8(+) T cells and displayed improved antitumor potential upon adoptive transfer in murine lymphoma and melanoma models. Overall, this study delineates the metabolic configuration of CD8(+) T cells required for stable effector function in tumors and presents an affordable approach to promote the efficacy of CD8(+) T cells for adoptive T-cell therapy. SIGNIFICANCE: IL12-mediated metabolic reprogramming increases intracellular acetyl CoA to promote the effector function of CD8(+) T cells in nutrient-depleted tumor microenvironments, revealing strategies to potentiate the antitumor efficacy of T cells.
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE
Terms governing use and reproduction ©2022 The Authors; Published by the American Association for Cancer Research
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE
Terms governing use and reproduction https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
546 ## - LANGUAGE NOTE
Language note en
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN)
Topical term or geographic name as entry element Tumor Biology and Immunology
9 (RLIN) 1198
655 7# - INDEX TERM--GENRE/FORM
Genre/form data or focus term Text
Source of term local
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Kar, Anwesha
Relator term author
9 (RLIN) 1184
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Bhowmik, Debaleena
Relator term author
9 (RLIN) 1185
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Gautam, Anupam
Relator term author
9 (RLIN) 1186
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Basak, Debashree
Relator term author
9 (RLIN) 1187
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Sarkar, Ishita
Relator term author
9 (RLIN) 1188
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Ghosh, Puspendu
Relator term author
9 (RLIN) 1189
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Sarkar, Deborpita
Relator term author
9 (RLIN) 1190
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Deka, Alvina
Relator term author
9 (RLIN) 1191
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Chakraborty, Paramita
Relator term author
9 (RLIN) 1192
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Mukhopadhyay, Asima
Relator term author
9 (RLIN) 1193
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Mehrotra, Shikhar
Relator term author
9 (RLIN) 1194
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Basak, Soumen
Relator term author
9 (RLIN) 1195
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Paul, Sandip
Relator term author
9 (RLIN) 1196
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Chatterjee, Shilpak
Relator term author
9 (RLIN) 1197
786 0# - DATA SOURCE ENTRY
Note Cancer Res
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1158/0008-5472.CAN-21-4052">http://dx.doi.org/10.1158/0008-5472.CAN-21-4052</a>
Public note Connect to this object online.

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