Abstract
Background: Programmed death-1 ligand 1 (PD-L1) is one of the most important immunoregulatory molecules expressed on the cell surface of many cell types under a variety of physiological and pathological conditions. One of its key functions is the inhibition of T cell effector activities by binding with programmed death-1 (PD-1) expressed on the surface of activated T and B cells. After its binding, PD-1 inhibits signal transduction of the T cell and B cell receptors. This immunosuppressive mechanism is widely used by many tumors to escape the immune attack, thereby favoring tumor progression. The systemic administration of antibodies that block PD-L1/PD-1 interactions to cancer patients is demonstrating unprecedented clinical success. This efficacy is usually explained by the reactivation of tumor-infiltrating T cells that have been inactivated by PD-L1/PD-1 interactions. However, PD-L1 also transmits intracellular signals to cancer cells that favour their survival. This intrinsic intracellular signaling may significantly contribute to tumor growth by conferring cancer cells resistance to apoptotic stimuli including interferons.
Conclusion: Here we review the current knowledge on PD-L1 signal transduction in cancer cells and its role in tumor progression and resistance to anti-cancer therapies.
Keywords: PD-L1, PDL1, B7-H1, CD274, immune checkpoint inhibitors, cancer immunotherapy, interferon, apoptosis.
Graphical Abstract
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