Monoamine oxidase blockade therapy for treating cancer through regulating antitumor t cell immunity

Abstract

Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain, where it breaks down neurotransmitters and thereby influences mood and behavior. While small molecule MAO inhibitors (MAOIs) have been developed used for treating depression and other neurological disorder, the involvement of MAO-A in antitumor immunity has not been known. The disclosure provided herein identifies MAO-A as an immune checkpoint and the use of MAOI antidepressants for cancer immunotherapy. Here we report induction of the Maoa gene in tumor-infiltrating immune cells. MAOI treatment significantly suppressed tumor growth in preclinical mouse syngeneic and human xenograft tumor models in a T cell-dependent manner. Combining MAOI and anti-PD-1 treatments generated synergistic tumor suppression effects. Clinical data correlation studies associated intratumoral MAOA expression with T cell dysfunction and impaired patient survival in a broad range of cancers.

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