Trogocytosis-Mediated CLDN18.2 Acquisition by CD8+ T Cells Impairs Anti-Tumor Immunity and Drives Pancreatic Cancer Progression

Highlight

– CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) acquire CLDN18.2 from tumor cells through trogocytosis, leading to impaired T cell activation and cytotoxicity.
– Trogocytosis-mediated CLDN18.2 expression suppresses glucose uptake and glycolysis in tumor-infiltrating CD8+ T cells by promoting β-catenin degradation.
– CLDN18.2+-dressed CD8+ T cells preferentially migrate to bone marrow, skew hematopoietic stem cells towards myeloid differentiation, and induce systemic immune senescence via IL1α.
– Targeting the CLDN18.2/β-catenin interaction with PC18.1 peptide improves immunotherapy response and inhibits PDAC progression in preclinical models.

Study Background and Disease Burden