Research ArticleIMMUNOTHERAPY

Targeting monoamine oxidase A for T cell–based cancer immunotherapy

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Science Immunology  14 May 2021:
Vol. 6, Issue 59, eabh2383
DOI: 10.1126/sciimmunol.abh2383

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Repurposing antidepressants for cancer immunotherapy

Antibodies targeting immune checkpoints that restrain the antitumor effects of T cells are now a proven therapeutic approach for many forms of human cancer. The search for additional drug-targetable checkpoint molecules that regulate tumor immunity continues. Wang et al. identified monoamine oxidase A (MAO-A) as a gene up-regulated in tumor-infiltrating immune cells in mice. Tumor cells grew at a slower rate in mutant mice with decreased MAO-A expression. Inhibition of MAO-A activity by the antidepressant drug phenelzine enhanced the resistance of wild-type mice to tumor growth and exhibited synergy with anti–PD-1 treatment. These findings set the stage for further studies assessing the potential of repurposed MAO-A inhibitor drugs in the immunotherapy of cancer.

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