A new strategy for CAR-T therapy in solid tumors: IL-15-autocrine signaling augments tumor stroma depletion and promotes a T_SCM subset in the TME.

ABSTRACT: Although chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable therapeutic effects in treating hematologic cancers, its effectiveness in solid tumors remains significantly restricted. the primary reason is the immunosuppression mediated by the tumor microenvironment (TME), which leads to rapid exhaustion of infiltrating CAR-T cells. To enhance CAR-T cell efficacy against solid tumors, we pursued improvements in two aspects. First, we constructed fibroblast activation protein (FAP)-directed CAR-T cells to enhance their anti-CAF capability within the TME, thereby alleviating the immunosuppressive barrier. Second, we utilized IL-15, an efficient activator of CAR-T cells that inhibits activation-induced cell death, restores effector functions, and increases the proportion of t

SUBMITTER: Pang Y 

PROVIDER: S-EPMC12808773 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature