Intrinsic PD-L1 in Tumor Progression

Programmed Cell Death Ligand 1 (PD-L1) is a glycoprotein molecule that is expressed on breast cancer cells, especially TNBC cells. PD-L1 expression is induced by oncogenic activation of signaling pathways such as PI3K/AKT, MAPK, and JAK/STAT. PD-L1 accelerates tumor progression by its extrinsic and intrinsic functions. Extrinsically, PD-L1 acts as an immunosuppressive molecule, causing T cell dysfunction by binding to the PD-1 receptor expressed on T cells, inhibiting their proliferation and triggering apoptosis, thereby protecting the tumor from cytotoxic T cell-mediated killing [10]. Intrinsically, PD-L1 expression strongly promotes cell proliferation through enhancing the survival and proliferation pathways. Although the correlation between PD-L1 and increased cell proliferation is established, the mechanism remains poorly understood. In this proposal, we will dissect the molecular mechanisms underlying PD-L1's intrinsic effects on cell proliferation.