Beyond its established role in immune suppression, PD-L1 demonstrates direct tumor-promoting functions in non-small cell lung cancer through a previously uncharacterized molecular mechanism. When Toll-like receptors are activated, PD-L1 enhances cancer cell growth and metastatic behavior by orchestrating autophagy via the TRAF6-BECN1 signaling cascade. CRISPR knockout experiments showed that removing PD-L1 significantly impaired tumor cell proliferation, migration, and three-dimensional growth, while overexpression produced the opposite effects. This discovery fundamentally reframes PD-L1 biology, revealing it functions as both an immune checkpoint and direct oncogenic driver. The finding has profound therapeutic implications, as current PD-L1 inhibitors like pembrolizumab may provide dual benefits—not only restoring immune surveillance but also directly disrupting tumor cell survival mechanisms. This could explain why some patients respond better to immunotherapy than immune status alone would predict. The research also suggests that combining autophagy inhibitors with PD-L1 blockers might enhance treatment efficacy, particularly in tumors with high PD-L1 expression that have developed resistance to conventional approaches.