Journal
PHARMACOLOGY & THERAPEUTICS
Volume 195, Issue -, Pages 162-171Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2018.11.004
Keywords
Cancer metabolism; Immunotherapy resistance; Warburg effect; Immune checkpoints; Tumor microenvironment
Categories
Funding
- American Lung Association Award [RG-514395]
- Cancer Center Support (Core) grant from National Cancer Institute, National Institutes of Health [CA016672]
Ask authors/readers for more resources
Many metabolic alterations, including the Warburg effect, occur in cancer cells that influence the tumor microenvironment, including switching to glycolysis from oxidative phosphorylation, using opportunistic modes of nutrient acquisition, and increasing lipid biosynthesis. The altered metabolic landscape of the tumor microenvironment can suppress the infiltration of immune cells and other functions of antitumor immunity through the production of immune-suppressive metabolites. Metabolic dysregulation in cancer cells further affects the expression of cell surface markers, which interferes with immune surveillance. Immune checkpoint therapies have revolutionized the standard of care for some patients with cancer, but disease in many others is. resistant to immunotherapy. Specific metabolic pathways involved in immunotherapy resistance include PI3K-Akt-mTOR, hypoxia-inducible factor (HIF), adenosine, JAK/STAT, and Wnt/Beta-catenin. Depletion of essential amino acids such as glutamine and tryptophan and production of metabolites like kynurenine in the tumor microenvironment also blunt immune cell function. Targeted therapies against metabolic checkpoints could work in synergy with immune checkpoint therapy. This combined strategy could be refined by profiling patients' mutation status before treatment and identifying the optimal sequencing of therapies. This personalized combinatorial approach, which has yet to be explored, may well pave the way for overcoming resistance to immunotherapy. (C) 2018 Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available