Immuno-metabolism: The role of cancer niche in immune checkpoint inhibitor resistance

Chao Yuan Weng; Cheng Xiang Kao; Te Sheng Chang; Yen Hua Huang

doi:10.3390/ijms22031258

Immuno-metabolism: The role of cancer niche in immune checkpoint inhibitor resistance

Chao Yuan Weng
, Cheng Xiang Kao
, Te Sheng Chang
, Yen Hua Huang

Research output: Contribution to journal › Review article › peer-review

29 Citations (Scopus)

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.

Original language	English
Article number	1258
Pages (from-to)	1-24
Number of pages	24
Journal	International journal of molecular sciences
Volume	22
Issue number	3
DOIs	https://doi.org/10.3390/ijms22031258
Publication status	Published - Feb 1 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cancer niche
Immune checkpoint in-hibitor
Immuno-metabolism
Immunotherapy
Metabolic reprogramming
Metabolism
Resistance
Tumor microenvironment

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms22031258

Cite this

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title = "Immuno-metabolism: The role of cancer niche in immune checkpoint inhibitor resistance",

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.",

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note = "Funding Information: Funding: This work was financially supported by research grants from the Ministry of Science and Technology, Taiwan (Grant numbers: MOST 107-2321-B-038-002, MOST 107-2314-B-038-061, MOST 108-2314-B-038-006, MOST 108-2321-B-038-003, MOST109-2314-B-038-135, MOST 109-2321-B-038-003, and MOST 109-2314-B-182-025). Funding Information: Acknowledgments: The authors acknowledge the academic and science graphic illustration service provided by the Office of Research and Development at Taipei Medical University. This manuscript was edited by Anita Infante. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Weng, Chao Yuan

AU - Kao, Cheng Xiang

AU - Chang, Te Sheng

AU - Huang, Yen Hua

N1 - Funding Information: Funding: This work was financially supported by research grants from the Ministry of Science and Technology, Taiwan (Grant numbers: MOST 107-2321-B-038-002, MOST 107-2314-B-038-061, MOST 108-2314-B-038-006, MOST 108-2321-B-038-003, MOST109-2314-B-038-135, MOST 109-2321-B-038-003, and MOST 109-2314-B-182-025). Funding Information: Acknowledgments: The authors acknowledge the academic and science graphic illustration service provided by the Office of Research and Development at Taipei Medical University. This manuscript was edited by Anita Infante. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

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KW - Immune checkpoint in-hibitor

KW - Immuno-metabolism

KW - Immunotherapy

KW - Metabolic reprogramming

KW - Metabolism

KW - Resistance

KW - Tumor microenvironment

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Immuno-metabolism: The role of cancer niche in immune checkpoint inhibitor resistance

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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