Regulation of T cell antitumor immune response by tumor induced metabolic stress

Authors:

Fanny Chalmin1,2,3,4, Mélanie Bruchard1,2,3,4, Frederique Vegran1,2,3,4 and Francois Ghiringhelli1,2,3,4
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Affiliations:

1 Cancer Biology Research Platform, Centre Georges-François Leclerc, Dijon, France.

2 Université de Bourgogne-Franche Comté.

3 GIMI Genetic and Immunology Medical Institute, Dijon, France.

4 INSERM UMR1231, Dijon, France.

Keywords: 

antitumor immmunity, metabolic stress, acidosis, hypoxia, amino acids, fatty acid, T cells.

Abbreviations:

HIF – hypoxia inducible factor,

IDO - indoleamine-2,3-dioxygenase,

LDH – lactate dehydrogenase,

PD-1 – programmed cell death 1,

PD-L1 – programmed death-ligand 1,

ROR – RAR-related orphan receptor,

TME – tumor microrenvironment,

Treg – regulatory T cell.

Corresponding Author(s):

Prof. François Ghiringhelli, Centre Georges François Leclerc, Genetic and Immunology Medical Institute GIMI, 1 rue du professeur Marion, 21000 Dijon, France. Phone: (33) 3-80-39-33-53; Fax: (33) 3-80-39-34-34 fghiringhelli@cgfl.fr

Conflict of interest statement:

Authors declare no conflict of interest relevant to this article.

Please cite this article as:

Fanny Chalmin, Mélanie Bruchard, Frederique Vegran and Francois Ghiringhelli (2019). Regulation of T cell antitumor immune response by tumor induced metabolic stress. Cell Stress 3(1): 9-18. doi: 10.15698/cst2019.01.171

© 2019 Chalmin et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy.