Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma
Kim I, Diamond M, Yuan S, Kemp S, Kahn B, Li Q, Lin J, Li J, Norgard R, Thomas S, Merolle M, Katsuda T, Tobias J, Baslan T, Politi K, Vonderheide R, Stanger B. Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma. Nature Communications 2024, 15: 1532. PMID: 38378697, PMCID: PMC10879147, DOI: 10.1038/s41467-024-46048-7.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaEpithelial-to-mesenchymal transitionResistance to immunotherapyT cell killingDuctal adenocarcinomaAcquired resistance to immunotherapyResistance to cancer immunotherapyMouse model of pancreatic ductal adenocarcinomaModel of pancreatic ductal adenocarcinomaExpression of immune checkpointsInterferon regulatory factor 6Effect of TNF-aEMT transcription factor ZEB1Antigen presentation machineryTumor immune microenvironmentCell-intrinsic defectsPro-apoptotic effectsPresentation machineryCancer immunotherapyImmune checkpointsTumor relapseImmune microenvironmentPrimary resistanceT cellsAcquired resistance