Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, Bhuvane S, Piper M, Gadwa J, Mueller AC, Nguyen D, Nangia V, Osborne DG, Bai X, Ferrara SE, Boss MK, Goodspeed A, Burchill MA, Tamburini BAJ, Chan ED, Pickering CR, Clambey ET, Karam SD. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. Journal For ImmunoTherapy Of Cancer 2021, 9: e001955. PMID: 33883256, PMCID: PMC8061827, DOI: 10.1136/jitc-2020-001955.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalBasic-Leucine Zipper Transcription FactorsCell Line, TumorCombined Modality TherapyDendritic CellsDrug Resistance, NeoplasmHead and Neck NeoplasmsImmune Checkpoint InhibitorsImmunotherapyInterleukin-2 Receptor alpha SubunitLymphocyte DepletionMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutPhenotypeRadiation Dose HypofractionationRadiation ToleranceRepressor ProteinsSquamous Cell Carcinoma of Head and NeckT-Lymphocytes, RegulatoryTumor BurdenTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsCombination radiation therapyRadiation therapyDendritic cellsLymph nodesMouse modelRadioresistant tumorsRegulatory T-cell depletionT cell effector responsesTumor-draining lymph nodesNeck squamous cell carcinomaOral squamous cell carcinoma tumorsT cell-dependent responsesSquamous cell carcinoma tumorsAnti-CD137 treatmentDC activation statusGy x 5Higher Treg numbersPlasticity of TregsAdoptive transfer studiesT-cell depletionSquamous cell carcinomaCell-dependent responsesOrthotopic mouse modelTumor necrosis factorαNew therapeutic opportunities