Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.
Molecular and Cellular Biology, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA.
Nat Commun. 2022 Jul 6;13(1):3882. doi: 10.1038/s41467-022-31417-x.
Mitochondrial dynamics can regulate Major Histocompatibility Complex (MHC)-I antigen expression by cancer cells and their immunogenicity in mice and in patients with malignancies. A crucial role in the mitochondrial fragmentation connection with immunogenicity is played by the IRE1α-XBP-1s axis. XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Mitochondrial fission inhibition with Mdivi-1 upregulates MHC-I expression on cancer cells and enhances the efficacy of adoptive T cell therapy in patient-derived tumor models. Therefore mitochondrial fission inhibition might provide an approach to enhance the efficacy of T cell-based immunotherapy.
线粒体动力学可以调节癌细胞中的主要组织相容性复合体（MHC）-I 抗原表达及其在小鼠和恶性肿瘤患者中的免疫原性。IRE1α-XBP-1s 轴在与免疫原性相关的线粒体片段连接中起着关键作用。XBP-1s 是氨肽酶 TPP2 的转录因子，它通过降解肿瘤抗原肽可能抑制 MHC-I 复合物细胞表面表达。用 Mdivi-1 抑制线粒体分裂可上调癌细胞上的 MHC-I 表达，并增强患者来源的肿瘤模型中过继 T 细胞治疗的疗效。因此，抑制线粒体分裂可能为提高基于 T 细胞的免疫疗法的疗效提供一种方法。
