State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
J Adv Res. 2023 Dec;54:147-179. doi: 10.1016/j.jare.2023.01.011. Epub 2023 Feb 2.
Tripartite motif (TRIM) family proteins have more than 80 members and are widely found in various eukaryotic cells. Most TRIM family proteins participate in the ubiquitin-proteasome degradation system as E3-ubiquitin ligases; therefore, they play pivotal regulatory roles in the occurrence and development of tumors, including tumor immune escape. Due to the diversity of functional domains of TRIM family proteins, they can extensively participate in multiple signaling pathways of tumor immune escape through different substrates. In current research and clinical contexts, immune escape has become an urgent problem. The extensive participation of TRIM family proteins in curing tumors or preventing postoperative recurrence and metastasis makes them promising targets.
The aim of the review is to make up for the gap in the current research on TRIM family proteins and tumor immune escape and propose future development directions according to the current progress and problems.
This up-to-date review summarizes the characteristics and biological functions of TRIM family proteins, discusses the mechanisms of TRIM family proteins involved in tumor immune escape, and highlights the specific mechanism from the level of structure-function-molecule-pathway-phenotype, including mechanisms at the level of protein domains and functions, at the level of molecules and signaling pathways, and at the level of cells and microenvironments. We also discuss the application potential of TRIM family proteins in tumor immunotherapy, such as possible treatment strategies for combination targeting TRIM family protein drugs and checkpoint inhibitors for improving cancer treatment.
三基序(TRIM)家族蛋白有 80 多个成员,广泛存在于各种真核细胞中。大多数 TRIM 家族蛋白作为 E3-泛素连接酶参与泛素蛋白酶体降解系统;因此,它们在肿瘤的发生和发展中发挥着关键的调节作用,包括肿瘤免疫逃逸。由于 TRIM 家族蛋白的功能结构域多样性,它们可以通过不同的底物广泛参与肿瘤免疫逃逸的多个信号通路。在当前的研究和临床背景下,免疫逃逸已成为一个紧迫的问题。TRIM 家族蛋白广泛参与肿瘤的治疗或预防术后复发和转移,这使得它们成为有前途的靶点。
本综述旨在弥补当前 TRIM 家族蛋白与肿瘤免疫逃逸研究的空白,并根据当前进展和问题提出未来的发展方向。
本最新综述总结了 TRIM 家族蛋白的特征和生物学功能,讨论了 TRIM 家族蛋白参与肿瘤免疫逃逸的机制,并从结构-功能-分子-途径-表型的层面突出了具体的机制,包括蛋白结构域和功能层面、分子和信号通路层面以及细胞和微环境层面的机制。我们还讨论了 TRIM 家族蛋白在肿瘤免疫治疗中的应用潜力,例如联合靶向 TRIM 家族蛋白药物和检查点抑制剂的可能治疗策略,以改善癌症治疗。