Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD40 AntigensCD8-Positive T-LymphocytesCytokinesDendritic CellsDisease Models, AnimalHumansImmunotherapyInterleukin-12MiceNeoplasmsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengePD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensBiopsyCD8-Positive T-LymphocytesEpidermisGene Expression ProfilingHumansImmune ToleranceLichen PlanusMiceProgrammed Cell Death 1 ReceptorSkinConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin tolerance