TY - JOUR
T1 - Immuno-metabolism
T2 - The role of cancer niche in immune checkpoint inhibitor resistance
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.
KW - Cancer niche
KW - Immune checkpoint in-hibitor
KW - Immuno-metabolism
KW - Immunotherapy
KW - Metabolic reprogramming
KW - Metabolism
KW - Resistance
KW - Tumor microenvironment
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U2 - 10.3390/ijms22031258
DO - 10.3390/ijms22031258
M3 - Review article
C2 - 33514004
AN - SCOPUS:85099969776
SN - 1661-6596
VL - 22
SP - 1
EP - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 3
M1 - 1258
ER -
