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...

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Bibliographic Details
Published in:Journal of oncology 2019, Vol.2019 (2019), p.1-12
Main Authors: Feichtinger, René G., Lang, Roland
Format: Article
Language:English
Subjects:
Antimitotic agents
Antineoplastic agents
Cancer
Carbon
Care and treatment
Dehydrogenases
Development and progression
Energy
Enzymes
Fibroblasts
Glucose
Hypotheses
Hypoxia
Immunotherapy
Melanoma
Metabolism
Metabolites
Metastasis
Mitochondria
Physiological aspects
Review
Transcription factors
Tumors
Vascular endothelial growth factor
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Summary: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.
ISSN:1687-8450
1687-8450
DOI:10.1155/2019/2084195