@article{10.1172/JCI152383, author = {Uta M. Demel AND Marlitt Böger AND Schayan Yousefian AND Corinna Grunert AND Le Zhang AND Paul W. Hotz AND Adrian Gottschlich AND Hazal Köse AND Konstandina Isaakidis AND Dominik Vonficht AND Florian Grünschläger AND Elena Rohleder AND Kristina Wagner AND Judith Dönig AND Veronika Igl AND Bernadette Brzezicha AND Francis Baumgartner AND Stefan Habringer AND Jens Löber AND Björn Chapuy AND Carl Weidinger AND Sebastian Kobold AND Simon Haas AND Antonia B. Busse AND Stefan Müller AND Matthias Wirth AND Markus Schick AND Ulrich Keller}, journal = {The Journal of Clinical Investigation}, publisher = {The American Society for Clinical Investigation}, title = {Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer}, year = {2022}, month = {5}, volume = {132}, url = {https://www.jci.org/articles/view/152383}, abstract = {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.}, number = {9}, doi = {10.1172/JCI152383}, url = {https://doi.org/10.1172/JCI152383}, }