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