Work

CD147 regulates CD8+ T cell cytotoxic activity by facilitating phosphorylation and subsequent recruitment of proximal TCR signaling kinases

Year: 2026

Type: article

Abstract: T cell-specific CD147 knockout model, we showed that CD147 loss significantly enhanced T cell cytotoxicity and reduced exhaustion. Mechanistically, CD147 promoted T cell exhaustion by disrupting proximal TCR kinase signaling through direct interactions with CD3ε, CD3ζ, and LCK, thereby promoting immune escape. Pharmacological inhibition with dasatinib attenuated CD147-driven overactivation and exhaustion. Furthermore, embedding the CD147 intracellular domain into CAR-T constructs significantly enhanced their cytotoxic efficacy while reducing exhaustion. These findings advance our understanding of T cell exhaustion in tumors and may inform strategies to optimize CAR-T therapy.

Source: iScience

DOI: 10.1016/j.isci.2026.114739