Serotonin transporter inhibits antitumor immunity through regulating the intratumoral serotonin axis

Identifying additional immune checkpoints hindering antitumor T cell responses is key to the development of next-generation cancer immunotherapies. Here, we report the induction of serotonin transporter (SERT), a regulator of serotonin levels and physiological functions in the brain and peripheral tissues, in tumor-infiltrating CD8 T cells. Inhibition of SERT using selective serotonin reuptake inhibitors (SSRIs), the most widely prescribed antidepressants, significantly suppressed tumor growth and enhanced T cell antitumor immunity in various mouse syngeneic and human xenograft tumor models. Importantly, SSRI treatment exhibited significant therapeutic synergy with programmed cell death protein 1 (PD-1)…

• RH
  Robin Hood Foundation
• IC
  Indiana Clinical and Translational Sciences Institute
• TC
  Tower Cancer Research Foundation
• RH
  Rose Hills Foundation
• NI
  National Institutes of Health
• UO
  University of California, Los Angeles
• CF
  Center for AIDS Research, University of Washington
• NH
  National Heart, Lung, and Blood Institute
• NC
  National Cancer Institute

  Award: T32-CA009120
• NC
  National Center for Advancing Translational Sciences

  Award: UL1TR001881
• JC
  Jonsson Comprehensive Cancer Center
• EA
  Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
• CA
  Clinical and Translational Science Institute, University of California, Los Angeles
• CF
  Center for AIDS Research, University of California Los Angeles