دورية أكاديمية
Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer
| العنوان: | Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer |
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| المؤلفون: | Demel, U.M., Böger, M., Yousefian, S., Grunert, C., Zhang, L., Hotz, P.W., Gottschlich, A., Köse, H., Isaakidis, K., Vonficht, D., Grünschläger, F., Rohleder, E., Wagner, K., Dönig, J., Igl, V., Brzezicha, B., Baumgartner, F., Habringer, S., Löber, J., Chapuy, B., Weidinger, C., Kobold, S., Haas, S., Busse, A.B., Müller, S., Wirth, M., Schick, M., Keller, U. |
| بيانات النشر: | American Society for Clinical Investigation |
| سنة النشر: | 2022 |
| المجموعة: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| مصطلحات موضوعية: | Cancer Research, Topic 1: Genes, Cells and Cell-Based Medicine, Topic 3: Integrative Biomedicine |
| الوصف: | Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell-mediated immunosurveillance by suppressing the MHC class I (MHC-I) antigen-processing and presentation machinery (APM). Loss of the MHC-I APM is a frequent cause of resistance to cancer immunotherapies, and the pharmacological inhibition of SUMOylation (SUMOi) resulted in reduced activity of the transcriptional repressor scaffold attachment factor B (SAFB) and induction of the MHC-I APM. Consequently, SUMOi enhanced the presentation of antigens and the susceptibility of tumor cells to CD8+ T cell-mediated killing. Importantly, SUMOi also triggered the activation of CD8+ T cells and thereby drove a feed-forward loop amplifying the specific antitumor immune response. In summary, we showed that activated SUMOylation allowed tumor cells to evade antitumor immunosurveillance, and we have expanded the understanding of SUMOi as a rational therapeutic strategy for enhancing the efficacy of cancer immunotherapies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; other |
| اللغة: | English |
| العلاقة: | http://edoc.mdc-berlin.de/21599/1/21599oa.pdfTest; http://edoc.mdc-berlin.de/21599/2/21599suppl.zipTest; Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer. Demel, U.M. and Böger, M. and Yousefian, S. and Grunert, C. and Zhang, L. and Hotz, P.W. and Gottschlich, A. and Köse, H. and Isaakidis, K. and Vonficht, D. and Grünschläger, F. and Rohleder, E. and Wagner, K. and Dönig, J. and Igl, V. and Brzezicha, B. and Baumgartner, F. and Habringer, S. and Löber, J. and Chapuy, B. and Weidinger, C. and Kobold, S. and Haas, S. and Busse, A.B. and Müller, S. and Wirth, M. and Schick, M. and Keller, U. Journal of Clinical Investigation 132 (9): e152383. 2 May 2022 |
| DOI: | 10.1172/JCI152383 |
| الإتاحة: | https://doi.org/10.1172/JCI152383Test http://edoc.mdc-berlin.de/21599Test/ https://edoc.mdc-berlin.de/21599Test/ http://edoc.mdc-berlin.de/21599/1/21599oa.pdfTest http://edoc.mdc-berlin.de/21599/2/21599suppl.zipTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.8884565 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1172/JCI152383 |
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