关键词: 头颈部鳞状细胞癌, 程序性死亡受体-1, 程序性死亡受体-1配体, 免疫治疗, 程序性死亡受体-1抑制剂, 程序性死亡受体-1配体抑制剂, 纳武单抗, 派姆单抗, 度伐单抗, 阿特珠单抗

Abstract:

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor that seriously threatens human health and life. With increasing studies on the mechanism of tumor immune escape, programmed death receptor 1 (PD-1) and programmed death ligand receptor 1 (PD-L1) have been proven to be involved in tumor immune escape. The primary mechanism is that PD-1 recruits protein tyrosine phosphatase (SHP-2) to dephosphorylate downstream tyrosine kinase (SyK) and phosphatidylinositol 3-kinase (PI3K), thereby inhibiting downstream protein kinase B (AKT), extracellular regulated protein kinases (ERK) and other important signaling pathways, ultimately inhibiting T cell activation. In recent years, PD-1/PD-L1 inhibitors have become popular immunotherapies. Pembrolizumab and nivolumab have been approved for HNSCC patients by the U.S. Food and Drug Administration. Both durvalumab and atezolizumab are still in clinical trials, and published data show that both have certain safety and efficacy but still need much clinical data to support them. Meanwhile, the combination of PD-1/PD-L1 inhibitors with radiotherapy, chemotherapy and immunotherapy is still controversial in terms of clinical efficacy and adverse events, and further research is needed. However, serious immune-related adverse reactions limit the clinical application of PD-1/PD-L1 inhibitors, despite promising curative effects. Therefore, developing novel inhibitors and investigating stable and effective biomarkers and upstream and downstream signaling mechanisms are urgent issues.

Key words: head and neck squamous cell carcinoma, programmed death receptor 1, programmed death receptor ligand 1, immunotherapy, programmed death receptor 1 inhibitor, programmed death receptor ligand 1 inhibitor, Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab