单胺氧化酶A
免疫系统
癌症研究
免疫疗法
癌症免疫疗法
癌症
单胺类神经递质
医学
免疫学
单胺氧化酶
药理学
生物
血清素
内科学
酶
受体
生物化学
作者
Xi Wang,Bo Li,Yu Jeong Kim,Yu Chen Wang,Zhe Li,Jiaji Yu,Samuel Zeng,Xiaoya Ma,In Young Choi,Stefano Di Biase,Dori J. Smith,Yang Zhou,Yan Ruide Li,Jie Huang,Nicole Clarke,Angela To,Laura Gong,Alexander Pham,Heesung Moon,Matteo Pellegrini,Lili Yang
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-05-28
卷期号:6 (59)
被引量:28
标识
DOI:10.1126/sciimmunol.abh2383
摘要
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. Small-molecule MAO inhibitors (MAOIs) have been developed and are clinically used for treating depression and other neurological disorders. However, the involvement of MAO-A in antitumor immunity has not been reported. Here, we observed induction of the Maoa gene in tumor-infiltrating immune cells. Maoa knockout mice exhibited enhanced antitumor T cell immunity and suppressed tumor growth. 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 decreased patient survival in a broad range of cancers. We further demonstrated that MAO-A restrains antitumor T cell immunity through controlling intratumoral T cell autocrine serotonin signaling. Together, these data identify MAO-A as an immune checkpoint and support repurposing MAOI antidepressants for cancer immunotherapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI