The mechanism and research progress of drug resistance of PD-1/PD-L1 immunotherapy in tumors / 药学学报

ABSTRACT

Programmed cell death protein 1 (PD-1) is an important immunosuppressive molecule, which combines with programmed cell death 1 ligand 1 (PD-L1) to initiate programmed T-cell death, leading to immune escape of tumor cells. Immune checkpoint inhibitors kill tumor cells by blocking the binding of PD-1 to PD-L1 and reactivating the patient's own immune system. With the approval of anti-PD-1 monoclonal antibodies nivolumab, pembrolizumab and anti-PD-L1 monoclonal antibody atezolizumab by FDA for the treatment of melanoma, advanced non-small cell lung cancer and other cancers, cancer treatment has ushered in a new dawn. However, only 20% of patients achieved long-term efficacy after treatment, and most patients relapsed later. Therefore, it is significant to identify effective biomarkers and develop new targets to improve the response of patients to immunotherapy. This article reviews on the mechanism of action of anti-PD-1/PD-L1 drugs in tumors, potential biomarkers and the mechanism of acquired drug resistance, as well as combination therapy under research.