口腔疾病防治 ›› 2021, Vol. 29 ›› Issue (10): 706-710.DOI: 10.12016/j.issn.2096-1456.2021.10.010

• 综述 • 上一篇    下一篇

程序性死亡受体-1及其配体抑制剂在头颈部鳞状细胞癌免疫治疗的研究进展

曾飞1,2(),卢洁1,2,孙仁浩1,2,房义康1,2,禹雯怡2,杨芳2,赵璐2()   

  1. 1.大连医科大学口腔医学院,辽宁 大连(116044)
    2.青岛市市立医院口腔医学中心,山东 青岛(266011)
  • 收稿日期:2020-10-19 修回日期:2020-12-10 出版日期:2021-10-20 发布日期:2021-06-23
  • 通讯作者: 赵璐
  • 作者简介:曾飞,硕士研究生,Email: zengfei1110@163.com
  • 基金资助:
    国家自然科学基金面上项目(81670979)

Research progress on programmed death receptor 1/ ligand 1 inhibitor in immunotherapy of head and neck squamous cell carcinoma

ZENG Fei1,2(),LU Jie1,2,SUN Renhao1,2,FANG Yikang1,2,YU Wenyi2,YANG Fang2,ZHAO Lu2()   

  1. 1. Dalian Medical University School of Stomatology, Dalian 116044, China
    2. Qingdao Municipal Hospital Stomatology Center, Qingdao 266011, China
  • Received:2020-10-19 Revised:2020-12-10 Online:2021-10-20 Published:2021-06-23
  • Contact: Lu ZHAO
  • Supported by:
    General Projects of National Natural Science Foundation of China(81670979)

摘要:

头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)是一种恶性肿瘤,严重威胁人类的生命和健康。随着对肿瘤免疫逃逸机制研究的不断深入,程序性死亡受体-1(programmed death receptor 1,PD-1)及其配体(programmed death receptor ligand 1,PD-L1)参与肿瘤免疫逃逸已被证实,主要作用机制是PD-1募集蛋白酪氨酸磷酸酶SHP-2,使下游的脾酪氨酸激酶(spleen tyrosine kinase,SyK)和磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)去磷酸化,从而抑制下游蛋白激酶B(protein kinase B,AKT)、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)等重要信号通路,最终抑制T细胞活化,介导免疫逃逸。近年来,PD-1/PD-L1抑制剂成为免疫治疗研究热点。美国食品药品监督管理局已批准纳武单抗(Nivolumab)和派姆单抗(Pembrolizumab)作为HNSCC治疗药物;度伐单抗(Durvalumab)和阿特珠单抗(Atezolizumab)目前仍在临床试验阶段,已发表数据显示二者均具有一定安全性和疗效性,但仍需大量临床数据支持。同时,PD-1/PD-L1抑制剂联合放疗、化疗和免疫治疗等治疗方案的临床疗效和不良反应事件发生率尚存在争议,仍需进一步研究。虽然PD-1/PD-L1抑制剂免疫治疗疗效可观,但其副作用限制了其广泛使用,更安全有效的PD-1/PD-L1新型抑制剂及其上下游信号转导机制以及稳定有效的生物标志物有待进一步研究。

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

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