上海大学学报(自然科学版) ›› 2023, Vol. 29 ›› Issue (2): 224-.doi: 10.12066/j.issn.1007-2861.2476

• • 上一篇    下一篇

Wnt/b-连环蛋白通路在免疫检查点抑制剂耐药中 作用的研究进展

王晨越1;2;3, 吴莉沙1;2;3, 汤承博2;3, 王进2, 解伟2;3;4   

  1. 1. 上海理工大学 健康科学与工程学院, 上海 200093; 2. 上海健康医学院药学院, 上海 201318; 3. 上海健康医学院 上海市分子影像学重点实验室, 上海201318; 4. 上海理工大学 研究生院, 上海 200093
  • 出版日期:2023-04-30 发布日期:2023-05-18
  • 通讯作者: 解伟(1988|), 男, 副教授, 博士, 研究方向为生物工程重组蛋白的设计及活性研究、抗肿瘤双特异性抗 体的设计及肿瘤免疫治疗. E-mail: xiewei22400@126.com
  • 基金资助:
    上海市自然科学基金面上项目(23ZR1427400); 上海市卫生健康委员会科研项目(20214Y0516); 上海市 教育委员会和上海市教育发展基金会\晨光计划" 项目(18-CG72); 上海市分子影像学重点实验室建设项 目(18DZ2260400)

Progress in research on the role of the Wnt/b-catenin pathway in immune checkpoint inhibitor resistance

  1. 1. School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; 2. School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; 3. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; 4. Graduate School of University of Shanghai for Science and Technology, Shanghai 200093, China
  • Online:2023-04-30 Published:2023-05-18

摘要: Wnt/b-连环蛋白信号通路是癌症领域最热门的分子靶点之一, 与许多恶性肿瘤的 发生和发展密切相关. Wnt/b-连环蛋白信号通路还广泛应用于肿瘤免疫调节, 异常活化的 Wnt/b-连环蛋白与肿瘤免疫抑制微环境密切相关. 目前, 免疫检查点抑制剂的研究和应用已 相当广泛, 但是以靶向程序性死亡受体1 (programmed cell death protein 1, PD-1)/程序性死 亡配体1 (programmed cell death ligand 1, PD-L1) 和细胞毒性T 淋巴细胞抗原4 (cytotoxic T lymphocyte antigen-4, CTLA-4) 为代表的免疫检查点抑制剂存在患者响应率低和耐药的 问题. Wnt/b-连环蛋白的激活会抑制肿瘤微环境CD8+ T 细胞的浸润, 抑制抗肿瘤免疫反应 并诱导免疫检查点抑制剂耐药. 重点讨论了Wnt/b-连环蛋白信号通路与免疫检查点的关系, 并对Wnt/b-连环蛋白抑制剂联合免疫检查点抑制剂治疗恶性肿瘤的研究进展进行综述.

关键词: Wnt/b-连环蛋白信号通路, 免疫检查点, 免疫逃逸, 免疫抑制微环境

Abstract: The Wnt/b-catenin signaling pathway has been one of the most common molec- ular targets of cancer treatment, owing to its involvement in the formation and development of many malignant tumors. It is also signi¯cantly involved in tumor immunoregulation, and abnormally activated Wnt/b-catenin signaling is closely linked to the immunosuppressive microenvironment of tumors. Immune checkpoint inhibitors have been widely studied and used for cancer treatment, but using inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) results in tumor drug resistance and low patient response rates. Activation of the Wnt/b-catenin pathway inhibits CD8+ T cell in¯ltration into the tumor microenviron- ment, which inhibits anti-tumor immune response and induces immune checkpoint inhibitor resistance. This review focuses on the relationship between the Wnt/b-catenin signaling pathway and immune checkpoints and reviews the research progress on the treatment of malignant tumors utilizing a combination of Wnt/b-catenin and immune checkpoint in- hibitors.

Key words: Wnt/b-catenin signaling pathway, immune checkpoint, immune escape, immunosuppressive microenvironment

中图分类号: