Li Muchun, Zhang Xiaozhen, Bai Xueli, Liang Tingbo
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Oncol. 2022 Apr 14;12:862154. doi: 10.3389/fonc.2022.862154. eCollection 2022.
Tumor necrosis factor (TNF) receptor type II (TNFR2) is expressed in various tumor cells and some immune cells, such as regulatory T cells and myeloid-derived suppressing cells. TNFR2 contributes a lot to the tumor microenvironment. For example, it directly promotes the occurrence and growth of some tumor cells, activates immunosuppressive cells, and supports immune escape. Existing studies have proved the importance of TNFR2 in cancer treatment. Here, we reviewed the activation mechanism of TNFR2 and its role in signal transduction in the tumor microenvironment. We summarized the expression and function of TNFR2 within different immune cells and the potential opportunities and challenges of targeting TNFR2 in immunotherapy. Finally, the advantages and limitations of TNFR2 to treat tumor-related diseases are discussed, and the problems that may be encountered in the clinical development and application of targeted anti-TNFR2 agonists and inhibitors are analyzed.
肿瘤坏死因子(TNF)Ⅱ型受体(TNFR2)在多种肿瘤细胞和一些免疫细胞中表达,如调节性T细胞和髓源性抑制细胞。TNFR2对肿瘤微环境有很大影响。例如,它直接促进某些肿瘤细胞的发生和生长,激活免疫抑制细胞,并支持免疫逃逸。现有研究已证明TNFR2在癌症治疗中的重要性。在此,我们综述了TNFR2的激活机制及其在肿瘤微环境信号转导中的作用。我们总结了TNFR2在不同免疫细胞中的表达和功能,以及在免疫治疗中靶向TNFR2的潜在机遇和挑战。最后,讨论了TNFR2治疗肿瘤相关疾病的优势和局限性,并分析了靶向抗TNFR2激动剂和抑制剂在临床开发和应用中可能遇到的问题。