RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells

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RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells
 
Zhang, Zhengkui; Kong, Xiangjun; Ligtenberg, Maarten A.; van Hal-van Veen, Susan E.; Visser, Nils L.; de Bruijn, Beaunelle; Stecker, Kelly; van der Helm, Pim W.; Kuilman, Thomas; Hoefsmit, Esmée P.; Vredevoogd, David W.; Apriamashvili, Georgi; Baars, Beau; Voest, Emile E.; Klarenbeek, Sjoerd; Altelaar, Maarten; Peeper, Daniel S.
(2022) Cell Reports Medicine, volume 3, issue 6, pp. 1 - 25
(Article)
Abstract
Tumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8+ T cell antitumor activity. Although innate natural killer (NK) cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel ... read more
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Keywords: bystander killing, function-based genome-wide screens, immunotherapy resistance, NK cells, T cells, Tumor Escape, Ubiquitination, Killer Cells, Natural, Tumor Necrosis Factor-alpha/metabolism, Ubiquitin-Protein Ligases/genetics, General Biochemistry,Genetics and Molecular Biology, Research Support, Non-U.S. Gov't, Journal Article
DOI: https://doi.org/10.1016/j.xcrm.2022.100655
ISSN: 2666-3791
Publisher: Cell Press
Note: Funding Information: We thank all members of the Peeper laboratory for helpful discussions. We thank the Animal facility, Cytometry facility, and Genomics core facility of NKI for support. We thank Joleen Traets and Alex van Vliet for help with bioinformatic analyses, and Disha Rao for help with FACS analysis. This work was supported by LSH-TKI grant LSHM20019, Oncode TDF grant P2019-0060, and Oncode base funding to D.S.P. X.K. M.A.L. and D.S.P. conceived the project. X.K. and M.A.L. performed the screen. Z.Z. and T.K. performed bioinformatic analyses. M.A.L. B.d.B. and S.E.v.H.-v.V. performed in vivo experiments. P.W.v.d.H. E.E.V. and Z.Z. were responsible for organoids experiments. Z.Z. and X.K. performed all other experiments. K.E.S. and M.A. performed mass spectrometric analysis. S.K. performed the IHC quantification. N.L.V. S.E.v.H.-v.V. E.P.H. D.W.V. G.A. and B.B. provided technical support. G.A. assisted with statistical analyses. Z.Z. X.K. and D.S.P. wrote the manuscript. All authors revised and approved the manuscript. The project was supervised by D.S.P. D.S.P. is co-founder, shareholder, and advisor of Immagene. M.A.L. is co-founder, shareholder, and CEO of Immagene. The other authors declare no competing interests. Funding Information: We thank all members of the Peeper laboratory for helpful discussions. We thank the Animal facility, Cytometry facility, and Genomics core facility of NKI for support. We thank Joleen Traets and Alex van Vliet for help with bioinformatic analyses, and Disha Rao for help with FACS analysis. This work was supported by LSH -TKI grant LSHM20019 , Oncode TDF grant P2019-0060 , and Oncode base funding to D.S.P. Publisher Copyright: © 2022 Netherlands Cancer Institute Copyright © 2022 Netherlands Cancer Institute. Published by Elsevier Inc. All rights reserved.
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