Targeting Has2 to enhance anti-tumor immunity in pancreatic cancer via PD-L1 regulation

Pancreatic cancer is an aggressive malignancy with poor prognosis and limited treatment options. Recent advances in immunotherapy show potential for improving outcomes; however, therapeutic resistance remains a challenge. We demonstrate that Has2 is significantly upregulated in pancreatic cancer, correlating with poor prognosis, reduced infiltration of CD4+ and CD8+ T cells, and shorter survival. Mechanistically, HAS2 stabilizes PD-L1, a key immune checkpoint molecule, by modulating K6- and K63-linked ubiquitination, enhancing PD-L1 stability and suppressing immune responses.