Featured Publications
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisAgonistic CD40 Antibodies in Cancer Treatment
Djureinovic D, Wang M, Kluger HM. Agonistic CD40 Antibodies in Cancer Treatment. Cancers 2021, 13: 1302. PMID: 33804039, PMCID: PMC8000216, DOI: 10.3390/cancers13061302.Peer-Reviewed Original ResearchAgonistic CD40 antibodyCD40 antibodyDendritic cellsAntigen presentationClinical developmentEarly phase clinical trialsAgonist CD40 antibodyActivation of CD8Pro-inflammatory effectsAntigen-presenting cellsT cell functionRenal cell carcinomaAnti-tumor effectsPhase clinical trialsAnti-tumor activityT cell activationCancer Genome AtlasSystemic therapyCell carcinomaCostimulatory moleculesCD40 expressionClinical trialsPancreatic adenocarcinomaPreclinical modelsT cellsProfiling cancer testis antigens in non–small-cell lung cancer
Djureinovic D, Hallström B, Horie M, Mattsson J, La Fleur L, Fagerberg L, Brunnström H, Lindskog C, Madjar K, Rahnenführer J, Ekman S, Ståhle E, Koyi H, Brandén E, Edlund K, Hengstler J, Lambe M, Saito A, Botling J, Pontén F, Uhlén M, Micke P. Profiling cancer testis antigens in non–small-cell lung cancer. JCI Insight 2016, 1: e86837. PMID: 27699219, PMCID: PMC5033889, DOI: 10.1172/jci.insight.86837.Peer-Reviewed Original ResearchConceptsCell lung cancerLung cancerCancer testisCTA expressionDifferent normal organsProtein expressionCancer Genome AtlasImmunotherapeutic strategiesPrognostic impactNSCLC casesNSCLC tissuesSurvival associationsNew CTANormal organsBiomarker studiesClinical interestCancerGenome AtlasReliable CTACTANSCLCConcurrent expressionRNAseq dataValuable targetStringent criteriaA pathology atlas of the human cancer transcriptome
Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk J, Brunnström H, Glimelius B, Sjöblom T, Edqvist P, Djureinovic D, Micke P, Lindskog C, Mardinoglu A, Ponten F. A pathology atlas of the human cancer transcriptome. Science 2017, 357 PMID: 28818916, DOI: 10.1126/science.aan2507.Peer-Reviewed Original ResearchConceptsRegulation of genesGenome-scale metabolic modelProtein-coding genesGenome-wide transcriptomeHuman cancer transcriptomeGenome-wide explorationCellular differentiationIndividual proteinsCancer transcriptomeMolecular mechanismsMetabolic modelsCell growthGenesTranscriptomeOpen-access databaseSystem-level approachMajor cancer typesMetabolic heterogeneityPathology AtlasGeneral patternCancer typesRegulationShorter patient survivalIndividual tumorsProtein
2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024 PMID: 39561007, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine modelGP100 expression is variable in intensity in melanoma
Mann J, Hasson N, Su D, Adeniran A, Smalley K, Djureinovic D, Jilaveanu L, Schoenfeld D, Kluger H. GP100 expression is variable in intensity in melanoma. Cancer Immunology, Immunotherapy 2024, 73: 191. PMID: 39105816, PMCID: PMC11303354, DOI: 10.1007/s00262-024-03776-5.Peer-Reviewed Original ResearchConceptsGp100 expressionCutaneous melanomaTreatment of cutaneous melanomaAdvanced cutaneous melanomaT-cell engagersImprove patient selectionMetastatic melanomaUveal melanomaMetastatic samplesPatient selectionClinical trialsMelanomaQuantitative immunofluorescence methodGp100Improve outcomesImmunofluorescence methodTherapeutic intentDrugCellular productsExpressionTebentafuspImmunohistochemistryMelanocortin-1 Receptor Expression as a Marker of Progression in Melanoma
Su D, Djureinovic D, Schoenfeld D, Marquez-Nostra B, Olino K, Jilaveanu L, Kluger H. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precision Oncology 2024, 8: e2300702. PMID: 38662983, PMCID: PMC11513442, DOI: 10.1200/po.23.00702.Peer-Reviewed Original ResearchConceptsMC1R expressionMelanoma progressionAssociated with shorter survivalStages of melanoma progressionCases of benign neviChronic sun exposureMarkers of progressionHuman melanoma tissuesBreslow thicknessMelanocortin-1Metastatic melanomaOverall survivalPrimary melanomaMetastatic tumorsMelanoma cohortReceptor expressionPredictive biomarkersAggressive melanomaPrimary lesionTissue microarrayShorter survivalMale sexQuantitative immunofluorescenceBenign neviClinical trialsDigital 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
1070 ‘Decoy-resistant’ IL-18 in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma
Schoenfeld D, Djureinovic D, Zhang L, Mann J, Huck J, Jilaveanu L, Ring A, Kluger H. 1070 ‘Decoy-resistant’ IL-18 in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma. 2023, a1177-a1179. DOI: 10.1136/jitc-2023-sitc2023.1070.Peer-Reviewed Original ResearchA modified IL-18 drug in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma
Schoenfeld D, Djureinovic D, Zhang L, Mann J, Huck J, Jilaveanu L, Ring A, Kluger H. A modified IL-18 drug in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma. The Oncologist 2023, 28: s7-s7. PMCID: PMC10445567, DOI: 10.1093/oncolo/oyad216.010.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaImmune cell depletion studiesCell depletion studiesT cellsAnti-tumor activityPreclinical modelsRENCA modelTumor growthNK cellsIL-18IL-18BPCell carcinomaAnti-PD-1/CTLAAnti-PD-1 therapyIntra-tumoral T cellsModest anti-tumor activityAnti-tumor immune responseCytokine/chemokine levelsCytokine/chemokine profilingDepletion studiesEarly phase clinical trialsDecoy receptor proteinEnrichment of CD8PD-1 blockadeImmune 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 samplesExpression of cancer–testis antigens in the immune microenvironment of non‐small cell lung cancer
Hikmet F, Rassy M, Backman M, Méar L, Mattsson J, Djureinovic D, Botling J, Brunnström H, Micke P, Lindskog C. Expression of cancer–testis antigens in the immune microenvironment of non‐small cell lung cancer. Molecular Oncology 2023, 17: 2603-2617. PMID: 37341056, PMCID: PMC10701773, DOI: 10.1002/1878-0261.13474.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCancer-testis antigensCell lung cancerImmune microenvironmentLung cancerT cellsCTA expressionAnti-cancer immune responseMost NSCLC casesEfficacy of immunotherapyPlasma cell infiltrationRegulatory T cellsImmune cell densityCellular immune reactionsNSCLC patientsImmune profileClinical outcomesNSCLC casesCell infiltrationImmune cellsImmunohistochemical profilingM2 macrophagesClinical dataImmune responseImmune reactionsPeripheral blood immune cell and cytokine profiling of patients receiving corticosteroids for immune checkpoint inhibitor-related adverse events: Steroid dose and duration.
Merkin R, Schoenfeld D, Djureinovic D, Austin M, Wang M, Qu R, Zhang L, Mann J, Wei W, Sun L, Aizenbud L, Destina J, Kluger H. Peripheral blood immune cell and cytokine profiling of patients receiving corticosteroids for immune checkpoint inhibitor-related adverse events: Steroid dose and duration. Journal Of Clinical Oncology 2023, 41: e14694-e14694. DOI: 10.1200/jco.2023.41.16_suppl.e14694.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsSevere immune-related adverse eventsPeripheral blood immune cellsBlood immune cellsSteroid therapyDose levelsSteroid taperAdverse eventsIL-6Immune cellsImmune checkpoint inhibitor-related adverse eventsSeverity of irAEsMultiple immune-related adverse eventsAnti-PD-1 therapyT effector memory cellsPeripheral blood mononuclear cellsYale Cancer CenterSerum cytokine concentrationsEffector memory cellsPathogenic T cellsBlood mononuclear cellsConcentrations of TNFαBiomarkers of responseT cell subtypesLenvatinib 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
2021
Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
Backman M, La Fleur L, Kurppa P, Djureinovic D, Elfving H, Brunnström H, Mattsson J, Lindberg A, Pontén V, Eltahir M, Mangsbo S, Gulyas M, Isaksson J, Jirström K, Kärre K, Leandersson K, Mezheyeuski A, Pontén F, Strell C, Lindskog C, Botling J, Micke P. Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer. The Journal Of Pathology 2021, 255: 243-256. PMID: 34339045, DOI: 10.1002/path.5772.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune cell infiltrationHigh immune cell infiltrationCell infiltrationNK cellsImmune classPlasma cellsLow immune cell infiltrationEra of immunotherapyCell lung cancerImmune cell markersTumor mutational loadImmune response-related genesInnate immune responseImmune cell analysisClinicopathologic characteristicsPD-L1Immune activationImmune classificationNSCLC casesImmune patternsLung cancerImmune cellsClinical backgroundImmune response
2020
Publisher Correction: A clonal expression biomarker associates with lung cancer mortality
Biswas D, Birkbak N, Rosenthal R, Hiley C, Lim E, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore D, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins T, Veeriah S, Wilson G, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan A, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C. Publisher Correction: A clonal expression biomarker associates with lung cancer mortality. Nature Medicine 2020, 26: 1148-1148. PMID: 32494065, DOI: 10.1038/s41591-020-0899-z.Peer-Reviewed Original Research
2019
A clonal expression biomarker associates with lung cancer mortality
Biswas D, Birkbak N, Rosenthal R, Hiley C, Lim E, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore D, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins T, Veeriah S, Wilson G, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan A, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C. A clonal expression biomarker associates with lung cancer mortality. Nature Medicine 2019, 25: 1540-1548. PMID: 31591602, PMCID: PMC6984959, DOI: 10.1038/s41591-019-0595-z.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerClinicopathological risk factorsCell lung cancerLung cancer mortalityPrognostic gene expression signaturesCancer cell proliferationGene expression signaturesCancer mortalityLung cancerRisk factorsExpression-based biomarkersCopy number gainsDisease subtypesClinical descriptorsTranscriptomic biomarkersIndividual tumorsCancer typesDiagnostic precisionMolecular biomarkersExpression signaturesCell proliferationDNA copy number gainsBiomarkersPatientsIntratumor heterogeneityMultiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung
Djureinovic D, Pontén V, Landelius P, Al Sayegh S, Kappert K, Kamali-Moghaddam M, Micke P, Ståhle E. Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung. BMC Cancer 2019, 19: 741. PMID: 31357969, PMCID: PMC6664554, DOI: 10.1186/s12885-019-5943-3.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAgedBlood ProteinsCarcinoembryonic AntigenCarcinoma, Non-Small-Cell LungChemokines, CXCCohort StudiesData AccuracyEarly Detection of CancerFemaleGPI-Linked ProteinsHumansImmunoassayLung NeoplasmsMaleMass ScreeningModels, BiologicalReceptor, ErbB-3ROC CurveSensitivity and SpecificityStatistics, NonparametricVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerProximity extension assayLung adenocarcinomaLung diseaseDisease groupNon-malignant lung diseasesEarly lung cancer detectionCell lung cancerDifferent lung diseasesDifferent plasma levelsMultiplex proximity extension assayHigh clinical relevanceNovel protein markersDifferent plasma concentrationsLocalized diseaseOverall prognosisSurgical resectionNSCLC patientsLung metastasesColorectal cancerLung cancerPlasma levelsTypical carcinoidLung conditionsLAC patientsPrognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
Edlund K, Madjar K, Mattsson J, Djureinovic D, Lindskog C, Brunnström H, Koyi H, Brandén E, Jirström K, Pontén F, Rahnenführer J, Micke P, Hengstler J. Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC. Journal Of Thoracic Oncology 2019, 14: 628-640. PMID: 30639618, DOI: 10.1016/j.jtho.2018.12.022.Peer-Reviewed Original ResearchConceptsPD-L1 positivityOverall survivalLymphocyte infiltrationSmoking historyPD-L1Prognostic associationPlasma cellsProgrammed Death Ligand 1 ExpressionTumor PD-L1 positivityDeath ligand 1 (PD-L1) expressionAssociation of lymphocytePositive immune cellsLigand 1 expressionPD-L1 axisPD-L1 statusMultivariate Cox regressionDeath ligand 1Longer overall survivalForkhead box P3Immune cell infiltrationShorter overall survivalPatients' smoking historyKaplan-Meier plotsCheckpoint inhibitorsNSCLC patients
2018
Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer
Djureinovic D, Dodig-Crnković T, Hellström C, Holgersson G, Bergqvist M, Mattsson J, Pontén F, Ståhle E, Schwenk J, Micke P. Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer. Lung Cancer 2018, 125: 157-163. PMID: 30429015, DOI: 10.1016/j.lungcan.2018.09.012.Peer-Reviewed Original ResearchConceptsCancer-testis antigensLung cancer patientsNSCLC patientsCancer patientsNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsLin-28 homolog BPresence of autoantibodiesCell lung cancerBenign lung diseasesDetection of autoantibodiesFamily member 3Immune targetsLung diseaseLung cancerNSCLC samplesImmune responseAutoantibodiesBenign groupPatientsBead arrayBead array technologyAntigenMember A (Fam46a) gene