TBB inhibits CK2/PD-L1/EGFR pathway-mediated tumor progression

The expression of PD-L1 on cancer cells facilitates tumor immune escape by binding to PD-1 on T cells, thereby inhibiting T cell activity. However, the role of intracellular PD-L1 signaling in tumor progression remains unclear. In this study, we demonstrate that CK2 induces PD-L1 phosphorylation at Thr-285, which enhances PD-L1 protein stability. This phosphorylation disrupts the interaction between LC3B and PD-L1, inhibiting PD-L1 degradation via autophagy. Furthermore, PD-L1-T285 phosphorylation promotes EGFR binding to PD-L1, leading to activation of EGFR downstream signaling. This activation drives non-small cell lung cancer (NSCLC) cell proliferation, migration, invasion, and tumor growth. Conversely, CK2 depletion or treatment with a CK2 inhibitor reversed these effects. Our findings reveal a novel mechanism by which the CK2/PD-L1/EGFR pathway promotes tumor progression.