Nihira Naoe Taira, Miki Yoshio
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
Front Oncol. 2022 Mar 23;12:825284. doi: 10.3389/fonc.2022.825284. eCollection 2022.
Tumor cells are eliminated by the immune system, including T lymphocytes and natural killer cells; however, many types of tumor cells acquire the immune tolerance by inhibiting T-cell activation and functions immune checkpoint molecules. Immunotherapy targeting immune checkpoint molecules such as Programmed death receptor 1 (PD-1)/Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) have shown successful outcomes for multiple cancer treatments, however some patients show the lack of durable responses. Thus, discovering the chemical compounds or drugs manipulating the expression or function of immune checkpoint molecules are anticipated to overcome the drug resistance of immune checkpoint inhibitors. Function of inhibitory immune checkpoint molecules is often dysregulated by the transcriptional and post-translational levels in tumors. Here, this review focuses on the post-translational modification of intrinsic PD-L1 functions and regulators for PD-L1 transcription.
肿瘤细胞可被免疫系统清除,包括T淋巴细胞和自然杀伤细胞;然而,许多类型的肿瘤细胞通过抑制T细胞活化和免疫检查点分子的功能获得免疫耐受。靶向程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)等免疫检查点分子的免疫疗法已在多种癌症治疗中取得成功,但一些患者显示出缺乏持久反应。因此,人们期望发现能够操纵免疫检查点分子表达或功能的化合物或药物,以克服免疫检查点抑制剂的耐药性。抑制性免疫检查点分子的功能在肿瘤中常常在转录和翻译后水平失调。在此,本综述聚焦于内源性PD-L1功能的翻译后修饰以及PD-L1转录的调节因子。