RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells
Zhengkui Zhang, Xiangjun Kong, Maarten A. Ligtenberg, Susan E. van Hal-van Veen, Nils L. Visser, Beaunelle de Bruijn, Kelly E. Stecker, Pim W. van der Helm, Thomas Kuilman, Esmée P. Hoefsmit, David W. Vredevoogd, Georgi Apriamashvili, Beau Baars, Emile E. Voest, Sjoerd Klarenbeek, Maarten Altelaar, Daniel S. Peeper
Abstract
T cell killing. This occurs in a tumor necrosis factor (TNF)-dependent manner, causing loss of A20 and non-canonical IKK complexes from TNF receptor complex I. A small-molecule RNF31 inhibitor sensitizes colon carcinoma organoids to TNF and greatly enhances bystander killing of MHC antigen-deficient tumor cells. These results merit exploration of RNF31 inhibition as a clinical pharmacological opportunity for immunotherapy-refractory cancers.