Targeting Intracellular Innate RNA-Sensing Systems Overcomes Resistance to CAR T-cell Therapy in Solid Tumors.

ABSTRACT: Despite the remarkable success of chimeric antigen receptor (CAR) T cells in certain hematologic malignancies, only modest responses have been achieved in solid tumors. Defective cell death pathways have recently been suggested as a tumor-intrinsic form of resistance to CAR T-cell treatment. In this study, we showed that insufficient activity of the innate RNA-sensing receptor system retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling protein (MAVS) leads to tumor cell-inherent resistance to CAR T-cell attack. Active RIG-I/MAVS signaling in tumor cells primed intrinsic mitochondrial apoptosis pathways and expression of cell death receptors, which funneled into CAR T-cell-triggered cell death. CAR T-cell reliance on tumor-intrinsic RIG-I signaling was observed in variou

SUBMITTER: Soliman N 

PROVIDER: S-EPMC12260516 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature