Trogocytosis-orchestrated CLDN18.2-"dressed" CD8+ T cells drive pancreatic cancer progression via glucose metabolic reprogramming-induced cytotoxicity debilitation and systematic immune senescence cas
3 months ago
- #immunotherapy
- #pancreatic cancer
- #trogocytosis
- CLDN18.2+CD8+ T cells are linked to poor pancreatic cancer prognosis and resistance to immunotherapy.
- CD8+ T cells acquire CLDN18.2 from tumor cells via trogocytosis, which inhibits their activation and cytotoxicity.
- CLDN18.2 suppresses glucose uptake, glycolysis, and cytotoxicity in tumor-infiltrating CD8+ T cells.
- Trogocytosis-related CLDN18.2 induces GSK3β/CK1α-mediated β-catenin phosphorylation, leading to its degradation in CD8+ T cells.
- CLDN18.2 interacts with β-catenin's N-terminal domain, enhancing its interaction with CK1α.
- CLDN18.2+CD8+ T cells migrate to the bone marrow via the CXCL12/CXCR4 axis, promoting myeloid differentiation and systemic immune senescence via IL1α.
- Preclinical studies show that PC18.1 peptide disrupts CLDN18.2/β-catenin interaction, sensitizing immunotherapy and suppressing PDAC progression.
- Targeting trogocytosis-related CLDN18.2+CD8+ T cells may be a promising therapeutic strategy for PDAC.