Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression.
Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression.
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线粒体分裂通过减少 MHC-I 表面表达诱导实体瘤中的免疫逃逸
DOI：
10.1038/s41467-022-31417-x
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发表时间：
2022-07-06
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体动力学可以调节癌细胞的主要组织相容性复合物（MHC）-I抗原表达及其在小鼠和恶性肿瘤患者中的免疫原性。IRE 1 α-XBP-1 s轴在与免疫原性相关的线粒体片段化中发挥关键作用。XBP-1 s是氨肽酶TPP 2的转录因子，其可能通过降解肿瘤抗原肽来抑制MHC-I复合物细胞表面表达。用Mdivi-1抑制线粒体分裂上调癌细胞上的MHC-I表达并增强患者来源的肿瘤模型中过继性T细胞疗法的功效因此，线粒体分裂抑制可能提供增强基于T细胞的免疫疗法的功效的方法。癌细胞下调主要组织相容性复合体I（MHC-I）的表面表达以用于免疫逃避。在这里，作者表明，快速线粒体分裂激活ER应激反应，导致实体癌细胞中MHC-I复合物形成和细胞表面表达减少;此外，线粒体分裂的抑制增加了小鼠模型中免疫介导的抗癌反应。
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. Cancer cells downregulate surface expression of major histocompatibility complex I (MHC-I) for immune evasion. Here, the authors show that rapid mitochondrial fission activates the ER-stress response leading to reduced MHC-I complex formation and cell surface expression in solid cancer cells; moreover inhibition of mitochondrial fission increases the immune-mediated anticancer response in murine models.
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影响因子：
15.9
作者：
DURSO, CM;WANG, ZG;FERRONE, S
通讯作者：
FERRONE, S
影响因子：
11.4
作者：
Brenner, D;Golks, A;Arnold, R
通讯作者：
Arnold, R
影响因子：
11.4
作者：
Baixauli, Francesc;Martin-Cofreces, Noa B.;Sanchez-Madrid, Francisco
通讯作者：
Sanchez-Madrid, Francisco
影响因子：
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Chen, Xi;Iliopoulos, Dimitrios;Zhang, Qing;Tang, Qianzi;Greenblatt, Matthew B.;Hatziapostolou, Maria;Lim, Elgene;Tam, Wai Leong;Ni, Min;Chen, Yiwen;Mai, Junhua;Shen, Haifa;Hu, Dorothy Z.;Adoro, Stanley;Hu, Bella;Song, Minkyung;Tan, Chen;Landis, Melissa D.;Ferrari, Mauro;Shin, Sandra J.;Brown, Myles;Chang, Jenny C.;Liu, X. Shirley;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.
影响因子：
16
作者：
Kashatus, Jennifer A.;Nascimento, Aldo;Myers, Lindsey J.;Sher, Annie;Byrne, Frances L.;Hoehn, Kyle L.;Counter, Christopher M.;Kashatus, David F.
通讯作者：
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