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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

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
Creator
Wang, Joy X.; Choi, Stephen Yiu Chuen; Niu, Xiaojia; Kang, Ning; Xue, Hui; Killam, James; Wang, Yuzhuo
Contributor
Vancouver Prostate Centre
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2020-11-07
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.
Subject
lactic acid; cancer-induced immunosuppression; epigenetic reprograming; de-differentiation; anticancer immunotherapy; acidic tumor microenvironment
Genre
Article
Type
Text
Language
eng
Date Available
2020-11-12
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0394945
URI
http://hdl.handle.net/2429/76497
Affiliation
Dentistry, Faculty of; Medicine, Faculty of; Other UBC; Non UBC; Urologic Sciences, Department of
Citation
International Journal of Molecular Sciences 21 (21): 8363 (2020)
Publisher DOI
10.3390/ijms21218363
Peer Review Status
Reviewed
Scholarly Level
Faculty
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0