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 featuresA 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 trials
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 blockersSingle-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 functionDistinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases.
Dhodapkar K, Boddupalli C, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar M. Distinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases. Journal Of Clinical Oncology 2017, 35: 3-3. DOI: 10.1200/jco.2017.35.7_suppl.3.Peer-Reviewed Original ResearchInhibitory immune checkpointsTissue-resident memory TT cellsIndividual metastasesMelanoma metastasesDominant T-cell receptorReduced T cell infiltrationTissue-resident memory phenotypeEffective anti-tumor immunityT-cell receptor sequencingTumor cellsExome sequencingResident memory phenotypeResident memory TT RM cellsAnti-tumor immunityT cell infiltrationCell receptor sequencingT cell subsetsAntibody-mediated blockadeT-cell contentVascular endothelial growth factorSingle-cell mass cytometryCell mass cytometryEndothelial growth factor
2016
Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells
Boddupalli CS, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM. Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight 2016, 1: e88955. PMID: 28018970, PMCID: PMC5161225, DOI: 10.1172/jci.insight.88955.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesMemory T cellsTissue-resident memory T cellsT cell receptorImmune checkpointsT cellsIndividual metastasesSubset of TILsExpression of ICsCell receptorTumor cellsLess IL-2Blood T cellsExpression of VEGFTIL infiltrationDurable responsesAdvanced melanomaImmune therapyNeoantigen loadIL-2Immune cellsNonlymphoid tissuesSame patientMyeloid cellsMetastasis
2015
Combination 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