2022
T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma
Lozano AX, Chaudhuri AA, Nene A, Bacchiocchi A, Earland N, Vesely MD, Usmani A, Turner BE, Steen CB, Luca BA, Badri T, Gulati GS, Vahid MR, Khameneh F, Harris PK, Chen DY, Dhodapkar K, Sznol M, Halaban R, Newman AM. T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma. Nature Medicine 2022, 28: 353-362. PMID: 35027754, PMCID: PMC8866214, DOI: 10.1038/s41591-021-01623-z.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune-related adverse eventsT-cell characteristicsIrAE developmentBlood samplesSevere immune-related adverse eventsAnti-PD-1 monotherapyCombination immune checkpoint inhibitorsT-cell receptor sequencingT cell abundanceCell receptor sequencingOrgan system involvementPeripheral blood samplesIrAE onsetCheckpoint inhibitorsAdverse eventsCheckpoint blockadeRNA sequencingTCR clonalityCombination therapyPatient cohortSystem involvementClinical managementTCR diversityImmunological state
2020
A proteomic biomarker discovery platform for predicting clinical benefit of immunotherapy in advanced melanoma.
Shaked Y, Harel M, Issler E, Fremder E, Jacob E, Dahan N, Bar H, Halaban R, Sznol M, Sharon O. A proteomic biomarker discovery platform for predicting clinical benefit of immunotherapy in advanced melanoma. Journal Of Clinical Oncology 2020, 38: 10037-10037. DOI: 10.1200/jco.2020.38.15_suppl.10037.Peer-Reviewed Original ResearchClinical benefitAdvanced melanomaMelanoma patientsTreatment modalitiesPD-1/PD-L1 axisAnti-PD-1 monotherapyCheckpoint inhibitor-based immunotherapyRemarkable clinical benefitAdvanced melanoma patientsPD-L1 axisImmune checkpoint inhibitor-based immunotherapyNon-responder groupNovel predictive biomarkerOngoing prospective studyPlasma samplesHost-mediated mechanismsHost-mediated responsesStable diseaseCancer treatment modalitiesClinical responseClinical outcomesEntire cohortProspective studyCombination therapyCTLA-4
2017
Future perspectives in melanoma research “Melanoma Bridge”, Napoli, November 30th–3rd December 2016
Ascierto PA, Agarwala SS, Ciliberto G, Demaria S, Dummer R, Duong CPM, Ferrone S, Formenti SC, Garbe C, Halaban R, Khleif S, Luke JJ, Mir LM, Overwijk WW, Postow M, Puzanov I, Sondel P, Taube JM, Thor Straten P, Stroncek DF, Wargo JA, Zarour H, Thurin M. Future perspectives in melanoma research “Melanoma Bridge”, Napoli, November 30th–3rd December 2016. Journal Of Translational Medicine 2017, 15: 236. PMID: 29145885, PMCID: PMC5691855, DOI: 10.1186/s12967-017-1341-2.Peer-Reviewed Original ResearchConceptsT-cell therapyCombination therapyMetastatic melanomaChemokine receptorsT cellsHoming capacitySurvival rateTumor-Infiltrating Lymphocyte TherapyStage IV melanoma patientsAdoptive T-cell therapyCell therapyBRAF inhibitor monotherapyImmune checkpoint blockersSetting of treatmentIdentification of patientsChimeric antigen receptorEfficient combination therapyEmpowerment of patientsOptimize treatment regimensDifferent therapeutic agentsMelanoma BridgeImmunotherapy agentsOutcome enhancementCheckpoint blockadeCheckpoint blockers
2015
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Kim H, Frederick DT, Levesque MP, Cooper ZA, Feng Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn MM, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai Z. Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation. Cell Reports 2015, 11: 1458-1473. PMID: 26027934, PMCID: PMC4681438, DOI: 10.1016/j.celrep.2015.04.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChromatography, LiquidDown-RegulationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHeterograftsHumansImmunoblottingImmunohistochemistryImmunoprecipitationJanus Kinase 1Mass SpectrometryMelanomaMiceMice, NudeProto-Oncogene Proteins B-rafRNA, Small InterferingTransfectionUbiquitin-Protein LigasesConceptsBRAF inhibitorsRTK expressionReceptor tyrosine kinasesRemarkable clinical responsesBRAFi-resistant melanomasInhibition of JAK1BRAFi-resistant tumorsClinical responseCombination therapyMost tumorsBRAF mutationsTumor specimensVivo xenograftsBRAFi resistanceMelanoma cellsElevated expressionMelanomaEGFRAdaptive resistanceTumorsRNF125MITF expressionTyrosine kinaseJAK1DownregulationCombination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects