2024
Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma
Su D, Schoenfeld D, Ibrahim W, Cabrejo R, Djureinovic D, Baumann R, Rimm D, Khan S, Halaban R, Kluger H, Olino K, Galan A, Clune J. Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma. Journal For ImmunoTherapy Of Cancer 2024, 12: e008646. PMID: 38519058, PMCID: PMC10961546, DOI: 10.1136/jitc-2023-008646.Peer-Reviewed Original ResearchConceptsCTLA-4 expression levelsCancer-associated fibroblastsAssociated with worse survivalExpression of immune checkpointsLAG-3 expressionDesmoplastic melanomaLymphoid aggregatesCTLA-4PD-1Immune checkpointsIntratumoral leukocytesLAG-3Tumor compartmentsWorse survivalCD20+B cellsIncreased expression of immune checkpointsProgrammed cell death protein 1Macrophage/monocyte markerSentinel lymph node positivityCell death protein 1Associated with poor prognosisLymph node positivityDense fibrous stromaPotential prognostic significanceCore of tumors
2023
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samplesLenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma model
2020
Systemic Therapy for Brain Metastases: Melanoma
Weiss S, Kluger H. Systemic Therapy for Brain Metastases: Melanoma. 2020, 235-244. DOI: 10.1007/978-3-030-42958-4_16.Peer-Reviewed Original ResearchMelanoma brain metastasesIntracranial response ratesBrain metastasesClinical trialsResponse rateAnti-PD-1 monotherapyCentral nervous system metastasesExtracranial metastatic sitesNervous system metastasesSystemic therapy approachesMultiple clinical trialsSystemic therapySystemic treatmentAdvanced melanomaImmune checkpointsMetastatic sitesTherapeutic challengePatient survivalMetastatic melanomaExtracranial sitesStereotactic radiosurgeryMetastasisMutant BRAFSignificant causeMEK inhibitionA phase I, open-label, multicenter, single-dose escalation and multi-dose study of a monoclonal antibody targeting CEACAM1 in subjects with selected advanced or recurrent malignancies.
Shapira R, Weber J, Geva R, Sznol M, Kluger H, Wong D, Liang B. A phase I, open-label, multicenter, single-dose escalation and multi-dose study of a monoclonal antibody targeting CEACAM1 in subjects with selected advanced or recurrent malignancies. Journal Of Clinical Oncology 2020, 38: 3094-3094. DOI: 10.1200/jco.2020.38.15_suppl.3094.Peer-Reviewed Original ResearchWeek regimenCEACAM1 expressionAnti-PD-1 therapyPhase 1/2 clinical trialCell adhesion molecule-1Drug-related AEsHigh CEACAM1 expressionPhase 2 doseSingle-dose escalationMedian overall survivalAnti-tumor responseMulti-dose studyBest overall responseAdhesion molecule-1Poor disease prognosisExhausted lymphocytesStable diseaseSevere AEsAdult patientsOverall survivalTim-3Frequent AEsImmune checkpointsRecurrent malignancyRecurrent cancerMelanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy
Margolin K, Davies M, Kluger H, Tawbi H. Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy. 2020, 1421-1454. DOI: 10.1007/978-3-030-05070-2_65.Peer-Reviewed Original ResearchMelanoma brain metastasesCentral nervous systemSystemic therapyClinical benefitMainstay of therapyUnique patient populationDuration of responseHigh response rateFuture drug developmentMelanoma metastaticBrain metastasesDevastating complicationDurable responsesImmune checkpointsImmune therapyPatient populationMetastatic melanomaEffective modalityStereotactic radiosurgeryNervous systemResponse rateTherapyMultidisciplinary approachDrug developmentMelanoma
2019
Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy
Margolin K, Davies M, Kluger H, Tawbi H. Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy. 2019, 1-34. DOI: 10.1007/978-3-319-46029-1_65-1.Peer-Reviewed Original ResearchMelanoma brain metastasesCentral nervous systemSystemic therapyClinical benefitMainstay of therapyUnique patient populationDuration of responseHigh response rateFuture drug developmentMelanoma metastaticBrain metastasesDevastating complicationDurable responsesImmune checkpointsImmune therapyPatient populationMetastatic melanomaEffective modalityStereotactic radiosurgeryNervous systemResponse rateTherapyMultidisciplinary approachDrug developmentMelanoma
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