2024
Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma
Lu B, Lucca L, Lewis W, Wang J, Nogueira C, Heer S, Rayon-Estrada V, Axisa P, Reeves S, Buitrago-Pocasangre N, Pham G, Kojima M, Wei W, Aizenbud L, Bacchiocchi A, Zhang L, Walewski J, Chiang V, Olino K, Clune J, Halaban R, Kluger Y, Coyle A, Kisielow J, Obermair F, Kluger H, Hafler D. Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma. Nature Immunology 2024, 1-10. PMID: 39609626, DOI: 10.1038/s41590-024-02023-4.Peer-Reviewed Original ResearchCD8+ T cellsAnti-tumor immunityRegulatory T cellsT cellsSubpopulation of CD8+ T cellsCytotoxic CD8+ T cellsHuman CD8+ T cellsTumor antigen-specific CD8Impaired anti-tumor immunityTumor antigen-specificPoor overall survivalTumor rejectionKIR expressionOverall survivalTumor antigensImmune evasionCellular mediatorsHuman cancersCD8MelanomaTumorTranscriptional programsFunctional heterogeneityImmunityPatientsInterferon-stimulated neutrophils as a predictor of immunotherapy response
Benguigui M, Cooper T, Kalkar P, Schif-Zuck S, Halaban R, Bacchiocchi A, Kamer I, Deo A, Manobla B, Menachem R, Haj-Shomaly J, Vorontsova A, Raviv Z, Buxbaum C, Christopoulos P, Bar J, Lotem M, Sznol M, Ariel A, Shen-Orr S, Shaked Y. Interferon-stimulated neutrophils as a predictor of immunotherapy response. Cancer Cell 2024, 42: 253-265.e12. PMID: 38181798, PMCID: PMC10864002, DOI: 10.1016/j.ccell.2023.12.005.Peer-Reviewed Original ResearchImmunotherapy responseNon-small cell lung cancerAnti-PD1 responseAnti-PD1 therapyCohort of patientsNon-responsive tumorsCell lung cancerAnti-cancer immunotherapyPre-clinical findingsBlood-borne biomarkersCytotoxic TLung cancerPredictive biomarkersCurrent biomarkersTreatment responseNeutrophilsLY6EBiomarkersActive biomarkersPatientsMiceFurther mechanistic understandingActivationResponseImmunotherapy
2023
CD4 T cells and toxicity from immune checkpoint blockade
Earland N, Zhang W, Usmani A, Nene A, Bacchiocchi A, Chen D, Sznol M, Halaban R, Chaudhuri A, Newman A. CD4 T cells and toxicity from immune checkpoint blockade. Immunological Reviews 2023, 318: 96-109. PMID: 37491734, PMCID: PMC10838135, DOI: 10.1111/imr.13248.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsIrAE developmentHigh-dose corticosteroid treatmentT-cell receptor sequencingT cell abundanceImmune checkpoint blockadeCD4 T cellsICI discontinuationCheckpoint inhibitorsCorticosteroid treatmentAdverse eventsCheckpoint blockadeAdvanced melanomaHospital admissionTreatment initiationRNA sequencingSafety profileCancer patientsTCR diversityT cellsBulk RNA sequencingSingle-cell RNA sequencingOrgan systemsPatientsBaseline features
2020
21 Plasma-based proteomic profiling as a tool for predicting response to immunotherapy in melanoma patients
Harel M, Lahav C, Jacob E, Issler E, Bar H, Dicker A, Sharon O, Bacchiocchi A, Halaban R, Sznol M, Shaked Y. 21 Plasma-based proteomic profiling as a tool for predicting response to immunotherapy in melanoma patients. Journal For ImmunoTherapy Of Cancer 2020, 8: a11-a12. DOI: 10.1136/jitc-2020-sitc2020.0021.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMelanoma patientsClinical outcomesHost responseNon-small cell lung cancerCell lung cancerNon-responder groupPlasma samplesPro-metastatic effectsAnti-tumor activityPredictive biomarker discoveryProteomic profilingPlasma proteomic analysisAnti-cancer therapyICI therapyCheckpoint inhibitorsRECIST criteriaLung cancerTreatment modalitiesMechanisms of resistanceIndependent cohortPatientsTumor progressionPredictive signatureImmunotherapy
2018
Early B cell changes predict autoimmunity following combination immune checkpoint blockade
Das R, Bar N, Ferreira M, Newman AM, Zhang L, Bailur JK, Bacchiocchi A, Kluger H, Wei W, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. Journal Of Clinical Investigation 2018, 128: 715-720. PMID: 29309048, PMCID: PMC5785243, DOI: 10.1172/jci96798.Peer-Reviewed Original ResearchConceptsCombination checkpoint blockadeB cell changesB cellsCheckpoint blockadeCell changesCombination immune checkpoint blockadeB-cell receptor sequencingRisk of irAEsImmune checkpoint blockadeCell receptor sequencingB cell activationTreatment-induced changesCCB therapyAdverse eventsPD1 expressionPD1 receptorGrade 3PatientsCell activationEarly changesSingle-cell RNA sequencingTherapyPreemptive strategyCancer therapyIrAEsA Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma
Weber JS, Sznol M, Sullivan RJ, Blackmon S, Boland G, Kluger HM, Halaban R, Bacchiocchi A, Ascierto PA, Capone M, Oliveira C, Meyer K, Grigorieva J, Asmellash SG, Roder J, Roder H. A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma. Cancer Immunology Research 2018, 6: 79-86. PMID: 29208646, DOI: 10.1158/2326-6066.cir-17-0412.Peer-Reviewed Original ResearchConceptsAcute phase reactantsCheckpoint inhibitorsOverall survivalPhase reactantsIpilimumab-treated patientsPD-1 blockadeTrials of nivolumabBetter overall survivalIndependent patient cohortsPretreatment serumPD-1Melanoma patientsValidation cohortMetastatic melanomaMultipeptide vaccinePatient cohortPooled analysisWorse outcomesClinical dataPatientsMultivariate analysisComplement cascadeMass spectrometry analysisNivolumabCohort
2017
ISY9-3 Proteomic and T cell biomarkers identify sensitivity and resistance to immunotherapy in cancer patients
Weber J, Woods D, Laino A, Kluger H, Halaban R, Sznol M, Roder H, Roder J, Blackmon K, Sullivan R. ISY9-3 Proteomic and T cell biomarkers identify sensitivity and resistance to immunotherapy in cancer patients. Annals Of Oncology 2017, 28: ix21. DOI: 10.1093/annonc/mdx553.001.Peer-Reviewed Original Research
2016
1055O Changes in serum IL8 levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small cell lung cancer patients
Sanmamed M, Perez-Gracia J, Fusco J, Oñate C, Perez G, Alfaro C, Martín-Algarra S, González A, Rodriguez-Ruiz M, Andueza M, Wang J, Bacchiocchi A, Halaban R, Kluger H, Sznol M, Melero I. 1055O Changes in serum IL8 levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small cell lung cancer patients. Annals Of Oncology 2016, 27: vi359. DOI: 10.1093/annonc/mdw378.03.Peer-Reviewed Original Research
2014
RAC1 and Melanoma
Halaban R. RAC1 and Melanoma. Clinical Therapeutics 2014, 37: 682-685. PMID: 25465943, PMCID: PMC4415501, DOI: 10.1016/j.clinthera.2014.10.027.Peer-Reviewed Original ResearchIdentification of PLX4032‐resistance mechanisms and implications for novel RAF inhibitors
Choi J, Landrette SF, Wang T, Evans P, Bacchiocchi A, Bjornson R, Cheng E, Stiegler AL, Gathiaka S, Acevedo O, Boggon TJ, Krauthammer M, Halaban R, Xu T. Identification of PLX4032‐resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell & Melanoma Research 2014, 27: 253-262. PMID: 24283590, PMCID: PMC4065135, DOI: 10.1111/pcmr.12197.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell Line, TumorCell ProliferationDNA Transposable ElementsDrug Resistance, NeoplasmHumansIndolesMAP Kinase Signaling SystemMelanomaModels, MolecularMolecular Sequence DataMutagenesis, InsertionalMutant ProteinsMutationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafSulfonamidesVemurafenibConceptsBRAF mutationsNovel BRAF mutationBRAF inhibitorsNext-generation BRAF inhibitorsPLX4032-resistant melanoma cellsMelanoma cellsMelanoma patient survivalHuman prostate cancerBRAF mutant cellsWhole-exome sequencingMelanoma patientsPatient survivalClinical trialsProstate cancerRAF inhibitorsOncogenic mutationsNew screening approachRelevant aberrationsInhibitorsCellsMutationsScreening approachNovel RAF inhibitorsPatientsPLX8394
2012
Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors
Shi H, Moriceau G, Kong X, Koya RC, Nazarian R, Pupo GM, Bacchiocchi A, Dahlman KB, Chmielowski B, Sosman JA, Halaban R, Kefford RF, Long GV, Ribas A, Lo RS. Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors. Cancer Discovery 2012, 2: 414-424. PMID: 22588879, PMCID: PMC3594852, DOI: 10.1158/2159-8290.cd-12-0022.Peer-Reviewed Original ResearchConceptsBRAF inhibitorsActivating mutationsObjective tumor responseMEK1/2 inhibitorMEK1 mutationsP-ERK1/2 levelsBRAF-mutant melanomaMelanoma cell linesAdvanced melanomaAntitumor responseExon 3 mutationsTumor responseDisease progressionMelanomaBRAFi resistanceDrug sensitivitySignificant alterationsPatientsCell linesInhibitorsBaselineMutationsExon 3Widespread use
2010
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
Rubinstein JC, Sznol M, Pavlick AC, Ariyan S, Cheng E, Bacchiocchi A, Kluger HM, Narayan D, Halaban R. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. Journal Of Translational Medicine 2010, 8: 67. PMID: 20630094, PMCID: PMC2917408, DOI: 10.1186/1479-5876-8-67.Peer-Reviewed Original ResearchConceptsV600K mutationsClinical trialsBRAF V600E/K mutationK mutationPotential therapeutic responseMutant BRAF inhibitorsBRAF inhibitor PLX4032BRAF V600K mutationMelanoma patientsTherapeutic responseBRAF mutationsPatientsV600E mutationInhibitor PLX4032BRAF kinasePLX4032TrialsCommon mutationsMutationsMelanomaIncidence
1987
Transplantation of Human Melanocytes
Lerner A, Halaban R, Klaus S, Moellmann G. Transplantation of Human Melanocytes. Journal Of Investigative Dermatology 1987, 89: 219-224. PMID: 3624895, DOI: 10.1111/1523-1747.ep12470973.Peer-Reviewed Original Research
1985
Primary Melanoma Cells of the Vertical Growth Phase: Similarities to Metastatic Cells2
Herlyn M, Balaban G, Bennicelli J, Guerry D, Halaban R, Herlyn D, Elder D, Maul G, Steplewski Z, Nowell P, Clark W, Koprowski H. Primary Melanoma Cells of the Vertical Growth Phase: Similarities to Metastatic Cells2. Journal Of The National Cancer Institute 1985, 74: 283-289. PMID: 3856042, DOI: 10.1093/jnci/74.2.283.Peer-Reviewed Original ResearchConceptsVertical growth phaseMetastatic melanoma cellsMelanoma cellsMetastatic lesionsPrimary melanomaMetastatic cellsMelanoma-associated antigensMixed hemadsorption assaysPrimary melanoma cellsLong-term cultured cellsMetastatic melanoma cell linesGrowth phaseMelanoma cell linesRadial growth phaseMalignant melanomaNude micePopulation-doubling timeNonrandom abnormalitiesFlow cytometryHemadsorption assaysMonoclonal antibodiesMelanomaPatientsCell linesLesions