TY  - JOUR
A1  - Demel, Uta M.
A1  - Böger, Marlitt
A1  - Yousefian, Schayan
A1  - Grunert, Corinna
A1  - Zhang, Le
A1  - Hotz, Paul W.
A1  - Gottschlich, Adrian
A1  - Köse, Hazal
A1  - Isaakidis, Konstandina
A1  - Vonficht, Dominik
A1  - Grünschläger, Florian
A1  - Rohleder, Elena
A1  - Wagner, Kristina
A1  - Dönig, Judith
A1  - Igl, Veronika
A1  - Brzezicha, Bernadette
A1  - Baumgartner, Francis
A1  - Habringer, Stefan
A1  - Löber, Jens
A1  - Chapuy, Björn
A1  - Weidinger, Carl Thomas Maximilian
A1  - Kobold, Sebastian
A1  - Haas, Simon
A1  - Busse, Antonia B.
A1  - Müller, Stefan
A1  - Wirth, Matthias
A1  - Schick, Markus
A1  - Keller, Ulrich
T1  - Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer
T2  - The Journal of Clinical Investigation
N2  - 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.
KW  - Immunology
KW  - Oncology
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62782
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-627829
SN  - 1558-8238
N1  - Part of the results shown here are based on data generated by the TCGA Research Network: http://cancergenome.nih.gov/. We thank Enio Gjerga for expert support with bioinformatics analysis. We thank the quantitative proteomics facility at IBC2 for performing MS measurements. This work was supported by Deutsche Forschungsgemeinschaft (DFG) grants SFB824/C3, SFB1335/P3, and KE 222/10-1, to UK; grant MU-1764/6, to SM; grant WO 2108/1-1, to EW; grant KO5055/2-1, to SK; and SFB-TRR 338/1 2021–452881907, to SK; Deutsche Krebshilfe (grants 70114425 and 70114724, to UK; grant 70114823, to SM); Stiftung Charité (to UK); the Wilhelm-Sander Foundation (2017.048.2, to UK); European Research Council grant 756017 (to SK); and the Marie-Sklodowska-Curie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer, funded by the H2020 Program of the European Union (grant 955575, to SK). UMD, FB, and S Habringer are participants in the BIH-Charité Junior Clinician Scientist program funded by the Charité – Universitätsmedizin Berlin and BIH.
VL  - 132
IS  - 9, art. e152383
SP  - 1
EP  - 16
PB  - American Society for Clinical Investigation
CY  - Ann Arbor, Mich
ER  -