Research Progress of PD-1 and Its Inhibitors in Tumor Immunotherapy

Programmed cell death protein 1 (PD-1) and its ligands PD-L1/PD-L2 serve as critical immune checkpoint molecules that execute core regulatory functions in tumor microenvironment-mediated immune evasion mechanisms. Recent clinical investigations have revealed that monoclonal antibody-based agents targeting this signaling axis demonstrate substantial antitumor efficacy across multiple malignancies. These therapeutic agents specifically block the PD-1/PD-L2 immunosuppressive pathway, thereby reversing the functional suppression of T lymphocytes. This discovery has translated into clinically validated immunotherapeutic strategies for diverse neoplastic diseases, including both solid tumors and hematologic malignancies. However, challenges such as drug resistance, cumulative toxicity, high treatment costs, and biomarker heterogeneity limit their widespread application. This article systematically reviews the structure of PD-1, the molecular mechanisms of the PD-1/PD-L1 signaling pathway, clinical treatment strategies (monotherapy, combined immunotherapy, combined traditional therapy, personalized treatment, and integration of novel therapies) and their challenges, while outlining future research directions to provide a theoretical basis for optimizing tumor immunotherapy.