2023
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 ResearchConceptsPD-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 challenge
2018
Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity
Perry CJ, Muñoz-Rojas AR, Meeth KM, Kellman LN, Amezquita RA, Thakral D, Du VY, Wang JX, Damsky W, Kuhlmann AL, Sher JW, Bosenberg M, Miller-Jensen K, Kaech SM. Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity. Journal Of Experimental Medicine 2018, 215: 877-893. PMID: 29436395, PMCID: PMC5839759, DOI: 10.1084/jem.20171435.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD40 AntigensCell ProliferationImmunotherapyInflammationInterferon-gammaMacrophagesMelanoma, ExperimentalMiceMyeloid CellsNeoplasmsPhenotypeProto-Oncogene Proteins B-rafPTEN PhosphohydrolaseReceptors, Granulocyte-Macrophage Colony-Stimulating FactorRNA, MessengerSurvival AnalysisT-LymphocytesTranscription, GeneticTumor Necrosis Factor-alphaConceptsCombination therapyEffective antitumor immune responseProtective T cell responsesTumor-associated myeloid cellsM2-like stateCheckpoint inhibitor therapyAntitumor immune responseT cell responsesCSF-1R inhibitorAntitumor immunityInhibitor therapySuch patientsIL-12IL-6Cancer immunotherapyTAM subsetsUntreated tumorsT cellsImmune responseMouse modelTherapeutic targetTAM subpopulationsMyeloid cellsTumor growthCell responses