2024
Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction
Li X, Liu T, Bacchiocchi A, Li M, Cheng W, Wittkop T, Mendez F, Wang Y, Tang P, Yao Q, Bosenberg M, Sznol M, Yan Q, Faham M, Weng L, Halaban R, Jin H, Hu Z. Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction. EMBO Molecular Medicine 2024, 16: 2188-2209. PMID: 39164471, PMCID: PMC11393307, DOI: 10.1038/s44321-024-00115-0.Peer-Reviewed Original ResearchMolecular residual diseaseCirculating tumor DNAWhole-genome sequencingCell-free DNAGenome sequenceDetection of molecular residual diseaseCirculating tumor DNA detectionResidual disease detectionConsistent with clinical outcomesVariant allele frequencyResidual diseaseMelanoma patientsMonitoring immunotherapyTumor DNAEsophageal cancerClinical outcomesColorectal cancerWGS technologiesAllele frequenciesCancerDNAAnalytical sensitivitySequenceImmunotherapyRelapse
2023
A subset of neutrophils as a predictive biomarker for immunotherapy response in patients with non–small-cell lung cancer and melanoma.
Shaked Y, Benguigui M, Halaban R, Bacchiocchi A, Kamer I, Bar J, Lotem M, Shen-Orr S, Sznol M, Cooper T. A subset of neutrophils as a predictive biomarker for immunotherapy response in patients with non–small-cell lung cancer and melanoma. Journal Of Clinical Oncology 2023, 41: 2557-2557. DOI: 10.1200/jco.2023.41.16_suppl.2557.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsCell lung cancerImmunotherapy outcomesImmunotherapy responseMelanoma patientsCancer patientsLung cancerT cellsImmune checkpoint inhibitor-based therapyNew biomarkersNon-small cell lung cancerAdvanced metastatic NSCLCAnti-PD1 responseImmunotherapy-treated patientsMyeloid cell compositionPDL-1 expressionSubset of neutrophilsAnti-PD1 therapyMalignant melanoma patientsBlood mononuclear cellsInhibitor-based therapyPre-clinical modelsRenal cell carcinomaBlood-borne biomarkersSuccessful clinical trialsDynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma
Lu L, Risch E, Halaban R, Zhen P, Bacchiocchi A, Risch H. Dynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma. International Immunopharmacology 2023, 118: 110092. PMID: 37004344, DOI: 10.1016/j.intimp.2023.110092.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeSoluble PD-L1 (sPD-L1) levelsPD-L1 ratioPD-L1 levelsSoluble PD-1Soluble PD-L1PD-L1PD-1Patient survivalSurvival statusPD-1/PD-L1Immune checkpoints PD-1T cell exhaustionPatients' survival statusSolid tumor typesInitial immunotherapyCheckpoint blockadeMelanoma patientsPoor prognosisRetrospective studyPatient responseCell exhaustionTumor typesMelanomaSurvival
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 signatureImmunotherapyA 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
2018
A 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
Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients
Sanmamed MF, Perez-Gracia JL, Schalper KA, Fusco JP, Gonzalez A, Rodriguez-Ruiz ME, Oñate C, Perez G, Alfaro C, Martín-Algarra S, Andueza MP, Gurpide A, Morgado M, Wang J, Bacchiocchi A, Halaban R, Kluger H, Chen L, Sznol M, Melero I. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients. Annals Of Oncology 2017, 28: 1988-1995. PMID: 28595336, PMCID: PMC5834104, DOI: 10.1093/annonc/mdx190.Peer-Reviewed Original ResearchConceptsSerum IL-8 levelsIL-8 levelsCell lung cancer patientsLung cancer patientsNSCLC patientsCancer patientsMelanoma patientsPD1/PD-L1 therapyAnti-PD-1 treatmentAnti-PD-1 blockadeSerum interleukin-8 levelsPD-L1 therapyImmune checkpoint blockadeInterleukin-8 levelsLonger overall survivalBiomarkers of responseMann-Whitney testCheckpoint blockadeFirst doseOverall survivalStrength of associationClinical benefitReceiver operation characteristic curveMetastatic melanomaSurrogate biomarkerSingle-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy.
Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Fan R, Halaban R, Zhou J. Single-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy. Journal Of Clinical Oncology 2017, 35: 49-49. DOI: 10.1200/jco.2017.35.7_suppl.49.Peer-Reviewed Original ResearchTumor-infiltrating T lymphocytesAnti-PD-1 therapyClinical outcomesCytokine profilingAnti-tumor T cell functionAnti-tumor T cell immunityTumor-infiltrating T cellsMIP-1 αAnti-tumor immunityT cell immunityResponse of patientsT cell functionCell immunityCheckpoint immunotherapyMelanoma patientsIL-8Metastatic melanomaCancer patientsTIL functionTIL analysisPatient responseT cellsT lymphocytesGranzyme BImmune function
2014
Future perspectives in melanoma research: meeting report from the "Melanoma Bridge", Napoli, December 5th-8th 2013
Ascierto PA, Grimaldi AM, Anderson AC, Bifulco C, Cochran A, Garbe C, Eggermont AM, Faries M, Ferrone S, Gershenwald JE, Gajewski TF, Halaban R, Hodi FS, Kefford R, Kirkwood JM, Larkin J, Leachman S, Maio M, Marais R, Masucci G, Melero I, Palmieri G, Puzanov I, Ribas A, Saenger Y, Schilling B, Seliger B, Stroncek D, Sullivan R, Testori A, Wang E, Ciliberto G, Mozzillo N, Marincola FM, Thurin M. Future perspectives in melanoma research: meeting report from the "Melanoma Bridge", Napoli, December 5th-8th 2013. Journal Of Translational Medicine 2014, 12: 277. PMID: 25348889, PMCID: PMC4232645, DOI: 10.1186/s12967-014-0277-z.Peer-Reviewed Original ResearchConceptsProlong progression-free survivalOverall survivalMelanoma patientsMetastatic melanomaPathway inhibitorTumor microenvironmentImmune-modulating antibodiesLigand 1 pathwayMelanoma Bridge meetingProgression-free survivalMetastatic melanoma patientsCell death 1Adoptive cell transferNovel therapeutic targetContemporary clinical managementImportance of biomarkersFuture drug developmentMitogen-activated protein kinase pathway inhibitorsDifferent immunotherapiesImmune inhibitoryMelanoma BridgeDurable responsesSystemic therapyDeath-1Immune therapyIdentification 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
2011
Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab
Yuan J, Adamow M, Ginsberg BA, Rasalan TS, Ritter E, Gallardo HF, Xu Y, Pogoriler E, Terzulli SL, Kuk D, Panageas KS, Ritter G, Sznol M, Halaban R, Jungbluth AA, Allison JP, Old LJ, Wolchok JD, Gnjatic S. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 16723-16728. PMID: 21933959, PMCID: PMC3189057, DOI: 10.1073/pnas.1110814108.Peer-Reviewed Original ResearchConceptsNY-ESO-1-seropositive patientsNY-ESO-1 antibodyT cell responsesClinical benefitImmune responseIpilimumab treatmentNY-ESO-1 immune responsesNY-ESO-1 serum antibodyTumor antigen-specific immune responsesCytotoxic T-lymphocyte antigen-4NY-ESO-1 immunityT-lymphocyte antigen-4Antigen-specific immune responsesIpilimumab-treated patientsAdvanced melanoma patientsAdvanced metastatic melanomaCancer/testis antigensSubset of patientsNY-ESO-1Significant survival advantageCD8 responsesAdoptive transferClinical outcomesMelanoma patientsProspective study
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
2004
Her2/neu is not a commonly expressed therapeutic target in melanoma – a large cohort tissue microarray study
Kluger HM, DiVito K, Berger AJ, Halaban R, Ariyan S, Camp RL, Rimm DL. Her2/neu is not a commonly expressed therapeutic target in melanoma – a large cohort tissue microarray study. Melanoma Research 2004, 14: 207-210. PMID: 15179190, DOI: 10.1097/01.cmr.0000130874.33504.2f.Peer-Reviewed Original ResearchConceptsHER2/neu expressionHER2/neuNeu expressionMelanoma specimensNeu stainingMelanoma patientsLarge cohortPositive HER2/neu expressionChemotherapy-resistant malignancyPrimary cutaneous lesionNumerous new agentsTissue microarray studyMonoclonal antibody trastuzumabAdjuvant therapyCutaneous specimensTrastuzumab therapyMetastatic lesionsBreslow depthClark levelClinicopathological dataCutaneous lesionsPrimary lesionTumor stageMetastatic melanomaBreast cancer