Cargando…

Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities

Although immunotherapy plays a significant role in tumor therapy, its efficacy is impaired by an immunosuppressive tumor microenvironment. A molecule that contributes to the protumor microenvironment is the metabolic product lactate. Lactate is produced in large amounts by cancer cells in response t...

Descripción completa

Detalles Bibliográficos
Autores principales: Feichtinger, René G., Lang, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875281/
https://www.ncbi.nlm.nih.gov/pubmed/31781212
http://dx.doi.org/10.1155/2019/2084195
_version_ 1783472993790328832
author Feichtinger, René G.
Lang, Roland
author_facet Feichtinger, René G.
Lang, Roland
author_sort Feichtinger, René G.
collection PubMed
description Although immunotherapy plays a significant role in tumor therapy, its efficacy is impaired by an immunosuppressive tumor microenvironment. A molecule that contributes to the protumor microenvironment is the metabolic product lactate. Lactate is produced in large amounts by cancer cells in response to either hypoxia or pseudohypoxia, and its presence in excess alters the normal functioning of immune cells. A key enzyme involved in lactate metabolism is lactate dehydrogenase (LDH). Elevated baseline LDH serum levels are associated with poor outcomes of current anticancer (immune) therapies, especially in patients with melanoma. Therefore, targeting LDH and other molecules involved in lactate metabolism might improve the efficacy of immune therapies. This review summarizes current knowledge about lactate metabolism and its role in the tumor microenvironment. Based on that information, we develop a rationale for deploying drugs that target lactate metabolism in combination with immune checkpoint inhibitors to overcome lactate-mediated immune escape of tumor cells.
format Online
Article
Text
id pubmed-6875281
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-68752812019-11-28 Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities Feichtinger, René G. Lang, Roland J Oncol Review Article Although immunotherapy plays a significant role in tumor therapy, its efficacy is impaired by an immunosuppressive tumor microenvironment. A molecule that contributes to the protumor microenvironment is the metabolic product lactate. Lactate is produced in large amounts by cancer cells in response to either hypoxia or pseudohypoxia, and its presence in excess alters the normal functioning of immune cells. A key enzyme involved in lactate metabolism is lactate dehydrogenase (LDH). Elevated baseline LDH serum levels are associated with poor outcomes of current anticancer (immune) therapies, especially in patients with melanoma. Therefore, targeting LDH and other molecules involved in lactate metabolism might improve the efficacy of immune therapies. This review summarizes current knowledge about lactate metabolism and its role in the tumor microenvironment. Based on that information, we develop a rationale for deploying drugs that target lactate metabolism in combination with immune checkpoint inhibitors to overcome lactate-mediated immune escape of tumor cells. Hindawi 2019-11-03 /pmc/articles/PMC6875281/ /pubmed/31781212 http://dx.doi.org/10.1155/2019/2084195 Text en Copyright © 2019 René G. Feichtinger and Roland Lang. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Feichtinger, René G.
Lang, Roland
Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities
title Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities
title_full Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities
title_fullStr Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities
title_full_unstemmed Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities
title_short Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities
title_sort targeting l-lactate metabolism to overcome resistance to immune therapy of melanoma and other tumor entities
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875281/
https://www.ncbi.nlm.nih.gov/pubmed/31781212
http://dx.doi.org/10.1155/2019/2084195
work_keys_str_mv AT feichtingerreneg targetingllactatemetabolismtoovercomeresistancetoimmunetherapyofmelanomaandothertumorentities
AT langroland targetingllactatemetabolismtoovercomeresistancetoimmunetherapyofmelanomaandothertumorentities