2023
Protocol for in vivo CRISPR screening using selective CRISPR antigen removal lentiviral vectors.
Lane-Reticker SK, Kessler EA, Muscato AJ, Kim SY, Doench JG, Yates KB, Manguso RT, Dubrot J. Protocol for in vivo CRISPR screening using selective CRISPR antigen removal lentiviral vectors. STAR Protoc 2023, 4: 102082. PMID: 36861834, DOI: 10.1016/j.xpro.2023.102082.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTargeting 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
In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer.
Dubrot J, Du PP, Lane-Reticker SK, Kessler EA, Muscato AJ, Mehta A, Freeman SS, Allen PM, Olander KE, Ockerman KM, Wolfe CH, Wiesmann F, Knudsen NH, Tsao HW, Iracheta-Vellve A, Schneider EM, Rivera-Rosario AN, Kohnle IC, Pope HW, Ayer A, Mishra G, Zimmer MD, Kim SY, Mahapatra A, Ebrahimi-Nik H, Frederick DT, Boland GM, Haining WN, Root DE, Doench JG, Hacohen N, Yates KB, Manguso RT. In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer. Nat Immunol 2022, 23: 1495-1506. PMID: 36151395, DOI: 10.1038/s41590-022-01315-x.Peer-Reviewed Original ResearchMutant 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
2021
In vivo screens using a selective CRISPR antigen removal lentiviral vector system reveal immune dependencies in renal cell carcinoma.
Dubrot J, Lane-Reticker SK, Kessler EA, Ayer A, Mishra G, Wolfe CH, Zimmer MD, Du PP, Mahapatra A, Ockerman KM, Davis TGR, Kohnle IC, Pope HW, Allen PM, Olander KE, Iracheta-Vellve A, Doench JG, Haining WN, Yates KB, Manguso RT. In vivo screens using a selective CRISPR antigen removal lentiviral vector system reveal immune dependencies in renal cell carcinoma. Immunity 2021, 54: 571-585.e6. PMID: 33497609, DOI: 10.1016/j.immuni.2021.01.001.Peer-Reviewed Original Research