Il-Kyu Kim, Mark S Diamond, Salina Yuan, Samantha B Kemp, Benjamin M Kahn, Qinglan Li, Jeffrey H Lin, Jinyang Li, Robert J Norgard, Stacy K Thomas, Maria Merolle, Takeshi Katsuda, John W Tobias, Timour Baslan, Katerina Politi, Robert H Vonderheide, Ben Z Stanger
Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using a mouse model of pancreatic ductal adenocarcinoma (PDAC) to study tumor relapse following immunotherapy-induced responses, we find that resistance is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), with EMT-transcription factors ZEB1 and SNAIL functioning as master genetic and epigenetic regulators of this effect. Acquired resistance in this model is not due to immunosuppression in the tumor immune microenvironment, disruptions in the antigen presentation machinery, or altered expression of immune checkpoints...
February 20, 2024: Nature Communications