Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity
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 a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8363 |
| _version_ | 1797548532599619584 |
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| author | Joy X. Wang Stephen Y.C. Choi Xiaojia Niu Ning Kang Hui Xue James Killam Yuzhuo Wang |
| author_facet | Joy X. Wang Stephen Y.C. Choi Xiaojia Niu Ning Kang Hui Xue James Killam Yuzhuo Wang |
| author_sort | Joy X. Wang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T15:01:52Z |
| format | Article |
| id | doaj.art-242fe24e363749b6a111394f6fe3c4ed |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:01:52Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-242fe24e363749b6a111394f6fe3c4ed2023-11-20T20:08:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012121836310.3390/ijms21218363Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer ImmunityJoy X. Wang0Stephen Y.C. Choi1Xiaojia Niu2Ning Kang3Hui Xue4James Killam5Yuzhuo Wang6Vancouver Prostate Centre, Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Vancouver, BC V6H 3Z6, CanadaDepartment of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, CanadaDepartment of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, CanadaDepartment of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, CanadaVancouver Prostate Centre, Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Vancouver, BC V6H 3Z6, CanadaImmune 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.https://www.mdpi.com/1422-0067/21/21/8363lactic acidcancer-induced immunosuppressionepigenetic reprogramingde-differentiationanticancer immunotherapyacidic tumor microenvironment |
| spellingShingle | Joy X. Wang Stephen Y.C. Choi Xiaojia Niu Ning Kang Hui Xue James Killam Yuzhuo Wang Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity International Journal of Molecular Sciences lactic acid cancer-induced immunosuppression epigenetic reprograming de-differentiation anticancer immunotherapy acidic tumor microenvironment |
| title | Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity |
| title_full | Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity |
| title_fullStr | Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity |
| title_full_unstemmed | Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity |
| title_short | Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity |
| title_sort | lactic acid and an acidic tumor microenvironment suppress anticancer immunity |
| topic | lactic acid cancer-induced immunosuppression epigenetic reprograming de-differentiation anticancer immunotherapy acidic tumor microenvironment |
| url | https://www.mdpi.com/1422-0067/21/21/8363 |
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