Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities.
Journal
Journal of oncology
ISSN: 1687-8450
Titre abrégé: J Oncol
Pays: Egypt
ID NLM: 101496537
Informations de publication
Date de publication:
2019
2019
Historique:
received:
09
05
2019
revised:
13
08
2019
accepted:
10
09
2019
entrez:
30
11
2019
pubmed:
30
11
2019
medline:
30
11
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31781212
doi: 10.1155/2019/2084195
pmc: PMC6875281
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
2084195Informations de copyright
Copyright © 2019 René G. Feichtinger and Roland Lang.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
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