2023
Targeting TBK1 to overcome resistance to cancer immunotherapy
Sun Y, Revach O, Anderson S, Kessler E, Wolfe C, Jenney A, Mills C, Robitschek E, Davis T, Kim S, Fu A, Ma X, Gwee J, Tiwari P, Du P, Sindurakar P, Tian J, Mehta A, Schneider A, Yizhak K, Sade-Feldman M, LaSalle T, Sharova T, Xie H, Liu S, Michaud W, Saad-Beretta R, Yates K, Iracheta-Vellve A, Spetz J, Qin X, Sarosiek K, Zhang G, Kim J, Su M, Cicerchia A, Rasmussen M, Klempner S, Juric D, Pai S, Miller D, Giobbie-Hurder A, Chen J, Pelka K, Frederick D, Stinson S, Ivanova E, Aref A, Paweletz C, Barbie D, Sen D, Fisher D, Corcoran R, Hacohen N, Sorger P, Flaherty K, Boland G, Manguso R, Jenkins R. Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature 2023, 615: 158-167. PMID: 36634707, PMCID: PMC10171827, DOI: 10.1038/s41586-023-05704-6.Peer-Reviewed Original ResearchConceptsOvercome resistance to cancer immunotherapyResistance to cancer immunotherapyPD-1 blockadeCancer immunotherapyImmune-evasion genesResponse to PD-1 blockadePatient-derived tumor modelsPatient-derived organoidsEffective treatment strategiesTBK1 inhibitionPD-1Effector cytokinesConcordant findingsTumor cellsTumor modelCaspase-dependent cell deathResponse to TNFTreatment strategiesTargeting TBK1ImmunotherapyPharmacological toolsBlockadeTumor spheroidsCell deathTBK1
2022
Mutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in CholangiocarcinomaMutant-IDH1 Promotes Immunoevasion in Cholangiocarcinoma
Wu M, Shi L, Dubrot J, Merritt J, Vijay V, Wei T, Kessler E, Olander K, Adil R, Pankaj A, Tummala K, Weeresekara V, Zhen Y, Wu Q, Luo M, Shen W, García-Beccaria M, Fernández-Vaquero M, Hudson C, Ronseaux S, Sun Y, Saad-Berreta R, Jenkins R, Wang T, Heikenwälder M, Ferrone C, Goyal L, Nicolay B, Deshpande V, Kohli R, Zheng H, Manguso R, Bardeesy N. Mutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in CholangiocarcinomaMutant-IDH1 Promotes Immunoevasion in Cholangiocarcinoma. Cancer Discovery 2022, 12: 812-835. PMID: 34848557, PMCID: PMC8904298, DOI: 10.1158/2159-8290.cd-21-1077.Peer-Reviewed Original ResearchConceptsTumor maintenanceKetoglutarate-dependent enzymesDiscovery of mechanismsDNA demethylaseResponse genesCell-specific ablationCTLA4 blockadeMouse modelEnzyme inhibitsImmune checkpoint activationCytotoxic T-cell functionTumor cellsSuppression of CD8T-cell depletionIssue featureT cell activityT cell recruitmentT cell functionNew therapeutic strategiesInterferon γ expressionIsocitrate dehydrogenase 1 (IDH1) mutationTET2Receptor 1Γ expressionInhibitor efficacy