Targeting ROS-sensing Nrf2 potentiates anti-tumor immunity of intratumoral CD8+ T and CAR-T cells
Yuna Jo, Ju A Shim, Jin Woo Jeong, Hyori Kim, So Min Lee, Juhee Jeong, Segi Kim, Sun‐Kyoung Im, Donghoon Choi, Byung Ha Lee, Yun Hak Kim, Chi Dae Kim, Chan Hyuk Kim, Changwan Hong
Abstract
T cells. Nrf2-deficient CTLs are resistant to ROS, and their effector functions are sustained in the TME. Furthermore, Nrf2 knockdown in human CAR-T cells enhanced the survival and function of intratumoral CAR-T cells in a solid tumor xenograft model and effectively controlled tumor growth. ROS-sensing Nrf2 inhibits the anti-tumor T cell responses, indicating that Nrf2 may be a potential target for T cell immunotherapy strategies against solid tumors.
Topics & Concepts
CTL*Cytotoxic T cellTumor microenvironmentCD8Cancer researchReactive oxygen speciesImmunologyBiologyImmune systemCancerFunction (biology)ImmunityCell biologyIn vitroGeneticsGenomics, phytochemicals, and oxidative stressImmune Cell Function and InteractionIL-33, ST2, and ILC Pathways