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Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity Wang, Joy X.; Choi, Stephen Yiu Chuen; Niu, Xiaojia; Kang, Ning; Xue, Hui; Killam, James; Wang, Yuzhuo, Ph.D.
Abstract
Immune evasion and altered metabolism, where glucose utilization is diverted to increased lactic acid production, are two fundamental hallmarks of cancer. Although lactic acid has long been considered a waste product of this alteration, it is now well accepted that increased lactic acid production and the resultant acidification of the tumor microenvironment (TME) promotes multiple critical oncogenic processes including angiogenesis, tissue invasion/metastasis, and drug resistance. We and others have hypothesized that excess lactic acid in the TME is responsible for suppressing anticancer immunity. Recent studies support this hypothesis and provide mechanistic evidence explaining how lactic acid and the acidic TME impede immune cell functions. In this review, we consider lactic acid’s role as a critical immunoregulatory molecule involved in suppressing immune effector cell proliferation and inducing immune cell de-differentiation. This results in the inhibition of antitumor immune responses and the activation of potent, negative regulators of innate and adaptive immune cells. We also consider the role of an acidic TME in suppressing anticancer immunity. Finally, we provide insights to help translate this new knowledge into impactful anticancer immune therapies.
Item Metadata
Title |
Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity
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Creator | |
Contributor | |
Publisher |
Multidisciplinary Digital Publishing Institute
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Date Issued |
2020-11-07
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Description |
Immune evasion and altered metabolism, where glucose utilization is diverted to increased lactic acid production, are two fundamental hallmarks of cancer. Although lactic acid has long been considered a waste product of this alteration, it is now well accepted that increased lactic acid production and the resultant acidification of the tumor microenvironment (TME) promotes multiple critical oncogenic processes including angiogenesis, tissue invasion/metastasis, and drug resistance. We and others have hypothesized that excess lactic acid in the TME is responsible for suppressing anticancer immunity. Recent studies support this hypothesis and provide mechanistic evidence explaining how lactic acid and the acidic TME impede immune cell functions. In this review, we consider lactic acid’s role as a critical immunoregulatory molecule involved in suppressing immune effector cell proliferation and inducing immune cell de-differentiation. This results in the inhibition of antitumor immune responses and the activation of potent, negative regulators of innate and adaptive immune cells. We also consider the role of an acidic TME in suppressing anticancer immunity. Finally, we provide insights to help translate this new knowledge into impactful anticancer immune therapies.
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Subject | |
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Type | |
Language |
eng
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Date Available |
2020-11-12
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Provider |
Vancouver : University of British Columbia Library
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Rights |
CC BY 4.0
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DOI |
10.14288/1.0394945
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URI | |
Affiliation | |
Citation |
International Journal of Molecular Sciences 21 (21): 8363 (2020)
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Publisher DOI |
10.3390/ijms21218363
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty
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DSpace
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Item Media
Item Citations and Data
Rights
CC BY 4.0