Plectin promotes an aggressive phenotype and represses cytotoxic T cell activity in pancreatic cancer

Background: Pancreatic adenocarcinoma (PDAC) is an abysmal disease, with a poor clinical outcome, largely due to limited life-extending treatments for patients. Notoriously, PDAC displays a T cell-suppressive tumor microenvironment where underlying molecular mechanisms that lead to this phenotype remain poorly understood. To unravel specific mechanisms, we utilized bioinformatic analyses with functional studies and revealed the cytolinker protein plectin (PLEC) as a novel player in regulating the T cell-suppressive tumor microenvironment of PDAC. Methods: patients. Functional validation was provided using a monoclonal antibody (mAb) against cell surface plectin (CSP) in two murine PDAC models to examine changes in tumor growth and immune cell subset abundance. Results: T cells were depleted, indicating that anti-CSP treatment is contingent on cytotoxic T cell functionality. Conclusion: . These findings position plectin as a high-priority therapeutic target, with the potential to fundamentally reshape immune responses in PDAC and improve outcomes for patients with few remaining options.