Trogocytosis-orchestrated CLDN18.2-"dressed" CD8(+) T cells drive pancreatic cancer progression via glucose metabolic reprogramming-induced cytotoxicity debilitation and systematic immune senescence cascade.

Trogocytosis-related CLDN18.2 impairs CD8(+) T cell cytotoxicity and promotes pancreatic cancer progression by degrading β-catenin and inducing immune senescence.

• Why it matters: Understanding how tumor-associated antigens like CLDN18.2 affect immune cell function is crucial for overcoming resistance to immunotherapy in pancreatic ductal adenocarcinoma (PDAC), a highly lethal cancer.
• What they did: Researchers used humanized, genetically engineered, and patient-derived models, along with flow cytometry, immunofluorescence, single-cell RNA sequencing, and IP-MS to investigate CLDN18.2's role in CD8(+) T cells and PDAC progression, focusing on trogocytosis and metabolic reprogramming.
• The result: Findings reveal that CLDN18.2 acquired via trogocytosis suppresses T cell glycolysis and cytotoxicity by promoting β-catenin degradation, and targeting this pathway with peptides enhances immunotherapy efficacy, offering a promising therapeutic approach.