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Review

Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance

by
Chao-Yuan Weng
1,2,
Cheng-Xiang Kao
2,3,
Te-Sheng Chang
4,5,* and
Yen-Hua Huang
2,3,6,7,8,9,10,11,*
1
School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
2
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
4
School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33382, Taiwan
5
Division of Internal Medicine, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan
6
TMU Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 11031, Taiwan
7
International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
8
TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
9
Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
10
Comprehensive Cancer Center of Taipei Medical University, Taipei 11031, Taiwan
11
PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
 
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(3), 1258; https://doi.org/10.3390/ijms22031258
Submission received: 30 December 2020 / Revised: 24 January 2021 / Accepted: 25 January 2021 / Published: 27 January 2021
(This article belongs to the Special Issue Immuno-Metabolism: Resisting Resistance to Immuno-Checkpoint Therapy)
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Abstract

The use of immune checkpoint inhibitors (ICI) in treating cancer has revolutionized the approach to eradicate cancer cells by reactivating immune responses. However, only a subset of patients benefits from this treatment; the majority remains unresponsive or develops resistance to ICI therapy. Increasing evidence suggests that metabolic machinery in the tumor microenvironment (TME) plays a role in the development of ICI resistance. Within the TME, nutrients and oxygen are scarce, forcing immune cells to undergo metabolic reprogramming to adapt to harsh conditions. Cancer-induced metabolic deregulation in immune cells can attenuate their anti-cancer properties, but can also increase their immunosuppressive properties. Therefore, targeting metabolic pathways of immune cells in the TME may strengthen the efficacy of ICIs and prevent ICI resistance. In this review, we discuss the interactions of immune cells and metabolic alterations in the TME. We also discuss current therapies targeting cellular metabolism in combination with ICIs for the treatment of cancer, and provide possible mechanisms behind the cellular metabolic rewiring that may improve clinical outcomes.
Keywords: metabolism; immuno-metabolism; metabolic reprogramming; immune checkpoint inhibitor; immunotherapy; resistance; tumor microenvironment; cancer niche metabolism; immuno-metabolism; metabolic reprogramming; immune checkpoint inhibitor; immunotherapy; resistance; tumor microenvironment; cancer niche

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MDPI and ACS Style

Weng, C.-Y.; Kao, C.-X.; Chang, T.-S.; Huang, Y.-H. Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance. Int. J. Mol. Sci. 2021, 22, 1258. https://doi.org/10.3390/ijms22031258

AMA Style

Weng C-Y, Kao C-X, Chang T-S, Huang Y-H. Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance. International Journal of Molecular Sciences. 2021; 22(3):1258. https://doi.org/10.3390/ijms22031258

Chicago/Turabian Style

Weng, Chao-Yuan, Cheng-Xiang Kao, Te-Sheng Chang, and Yen-Hua Huang. 2021. "Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance" International Journal of Molecular Sciences 22, no. 3: 1258. https://doi.org/10.3390/ijms22031258

APA Style

Weng, C.-Y., Kao, C.-X., Chang, T.-S., & Huang, Y.-H. (2021). Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance. International Journal of Molecular Sciences, 22(3), 1258. https://doi.org/10.3390/ijms22031258

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