PAK1 competitively binds to PD-L1, preventing its interaction with the E3 ligase TRIM21 and subsequent ubiquitination/degradation, and combined inhibition of PAK1 with anti-PD-1 therapy significantly improves pancreatic cancer treatment outcomes [150]—underscoring the potential of targeting PD-L1 stability regulators as combinatorial strategies to overcome immunotherapy resistance. Here, CD274 is linked to familial pancreatic carcinoma.