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 challengeBaseline skin cytokine profiles determined by RNA in situ hybridization correlate with response to dupilumab in patients with eczematous dermatitis
Singh K, Valido K, Swallow M, Okifo K, Wang A, Cohen J, Damsky W. Baseline skin cytokine profiles determined by RNA in situ hybridization correlate with response to dupilumab in patients with eczematous dermatitis. Journal Of The American Academy Of Dermatology 2023, 88: 1094-1100. PMID: 36780951, DOI: 10.1016/j.jaad.2022.12.052.Peer-Reviewed Original ResearchConceptsEczematous dermatitisHistologic featuresTreatment selectionType 1Type 3 inflammationInflammatory skin diseaseCertain histologic featuresSitu hybridization correlatesClinical responseNonresponder groupCytokine profileCytokine stainingAtopic dermatitisCytokine RNAEczematous disordersSitu hybridizationDupilumabIL13 expressionSkin diseasesType 2PatientsDermatitisNonrespondersMolecular heterogeneityImproved response