2024
CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells.
Pellegrino B, David K, Rabani S, Lampert B, Tran T, Doherty E, Piecychna M, Meza-Romero R, Leng L, Hershkovitz D, Vandenbark A, Bucala R, Becker-Herman S, Shachar I. CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells. PLOS Biology 2024, 22: e3002905. PMID: 39576827, DOI: 10.1371/journal.pbio.3002905.Peer-Reviewed Original ResearchTriple-negative breast cancerMacrophage migration inhibitory factorImmunosuppressive tumor microenvironmentTolerogenic dendritic cellsRegulatory B cellsChronic lymphocytic leukemiaTumor microenvironmentDendritic cellsImmune cellsB cellsBreast cancerInfiltration of immune cellsAggressive breast cancer subtypeMassive infiltration of immune cellsLevels of CD74Cytokine macrophage migration inhibitory factorBreast cancer subtypesMigration inhibitory factorBinding to CD74Naive BTol-DCsLymphocytic leukemiaTumor environmentMassive infiltrationCancer subtypesCauses of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era
Lee D, McNamara M, Yang A, Yaskolko M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Pigment Cell & Melanoma Research 2024, 37: 847-853. PMID: 39073002, DOI: 10.1111/pcmr.13188.Peer-Reviewed Original ResearchSite of metastasisPattern of metastatic diseaseMelanoma mortalityRetrospective observational cohort studyCause of cancer mortalityDistant lymph nodesObservational cohort studyDiagnosis to deathImmunotherapy eraAdvanced melanomaMetastatic diagnosisMetastatic diseaseMetastatic melanomaImmunotherapy treatmentRespiratory failureCause of deathMedian timeLymph nodesTherapeutic advancesCohort studyMelanomaImmunotherapyMechanism of deathPatientsEnd of lifePrognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma
Valdez C, Sánchez-Zuno G, Osmani L, Ibrahim W, Galan A, Bacchiocchi A, Halaban R, Kulkarni R, Kang I, Bucala R, Tran T. Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma. Oncotarget 2024, 15: 507-520. PMID: 39028303, PMCID: PMC11259151, DOI: 10.18632/oncotarget.28615.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkers, TumorFemaleHistocompatibility Antigens Class IIHumansImmune Checkpoint InhibitorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMelanomaMiddle AgedMutationPrognosisRetrospective StudiesSkin NeoplasmsConceptsMacrophage migration inhibitory factorImmune checkpoint inhibitionD-dopachrome tautomeraseExpression of macrophage migration inhibitory factorDrivers of tumor progressionInflammatory cell markersPatient tumor samplesPatient survival outcomesMigration inhibitory factorStatistically significant differenceCheckpoint inhibitionImmune therapyPrognostic valueSurvival outcomesResistant melanomaGene expressionImproved survivalRetrospective studyInflammatory markersTumor progressionCell markersTumor samplesClinical evidenceMelanomaBulk RNA sequencingPatterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 169: 555-561. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective studyCauses of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.
Lee D, Yang A, McNamara M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Journal Of Clinical Oncology 2024, 42: e21522-e21522. DOI: 10.1200/jco.2024.42.16_suppl.e21522.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsYale Cancer CenterAdvanced melanomaMetastatic diseaseMetastatic melanomaRespiratory failureSite of metastatic diseasePattern of metastatic diseaseDied of respiratory failureAnti-CTLA4 treatmentRetrospective observational cohort studyAnti-PD1 therapyDistant lymph nodesPatients aged >Site of diseaseSurvival of patientsObservational cohort studyMulti-system involvementDiagnosis to deathImmunotherapy eraAnti-PD1Checkpoint inhibitorsInstitutional review boardMetastatic sitesMetastatic diagnosisMIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy
Fey R, Nichols R, Tran T, Vandenbark A, Kulkarni R. MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy. Cancers 2024, 16: 1773. PMID: 38730725, PMCID: PMC11082995, DOI: 10.3390/cancers16091773.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune-related adverse events developmentResponse to ICB therapyImmune checkpoint blockade therapyImmune checkpoint blockadePredictive biomarkersICB therapyCheckpoint blockade therapySerum MIF levelsBlockade therapyCheckpoint blockadeMIF levelsMalignant melanomaTreatment resistanceSolid tumorsAdverse eventsAutoimmune diseasesContext of cancerPrognostic biomarkerCancer progressionCognate receptor CD74Receptor CD74TherapyCD74CancerMacrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities
Valdez C, Sánchez-Zuno G, Bucala R, Tran T. Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities. International Journal Of Molecular Sciences 2024, 25: 4849. PMID: 38732068, PMCID: PMC11084905, DOI: 10.3390/ijms25094849.Peer-Reviewed Original ResearchConceptsInhibition of MIFResponse to infectionNon-canonical signaling pathwaysClinical studiesCancer patientsClinical trialsInflammatory cytokinesDriving tumorigenesisClinical explorationCancer typesCancerDual inhibitionTherapeutic targetIn vivoIn vitroSignaling pathwayMIFAntitumor candidateBinding partnersVascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumorImmunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US
Kerekes D, Frey A, Prsic E, Tran T, Clune J, Sznol M, Kluger H, Forman H, Becher R, Olino K, Khan S. Immunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US. JAMA Oncology 2024, 10: 342-351. PMID: 38175659, PMCID: PMC10767643, DOI: 10.1001/jamaoncol.2023.6025.Peer-Reviewed Original ResearchNon-small cell lung cancerEnd of lifeMonth of deathImmunotherapy initiationCohort studyMAIN OUTCOMEStage IV non-small cell lung cancerCharlson-Deyo comorbidity indexHigh metastatic burdenInitiation of immunotherapyNational prescribing patternsRisk-adjusted patientsImmune checkpoint inhibitorsRetrospective cohort studyStage IV melanomaPercentage of patientsHigh-volume centersLocation of metastasesLow-volume centersOdds of deathCell lung cancerNational Clinical DatabaseLow-volume facilitiesDrug Administration approvalCheckpoint inhibitorsImmunotherapy utilization in stage IIIA melanoma: less may be more
Frey A, Kerekes D, Khan S, Tran T, Kluger H, Clune J, Ariyan S, Sznol M, Ishizuka J, Olino K. Immunotherapy utilization in stage IIIA melanoma: less may be more. Frontiers In Oncology 2024, 14: 1336441. PMID: 38380358, PMCID: PMC10876869, DOI: 10.3389/fonc.2024.1336441.Peer-Reviewed Original ResearchStage IIIA melanomaHigh-volume centersRisk-adjusted survivalLow-volume centersImmunotherapy utilizationAdjuvant immunotherapyStage IIIATreatment of stage III melanomaAcademic centersMultivariable Cox proportional hazards regressionStage III melanomaNational Cancer DatabaseStage III diseaseFactors associated with receiptCox proportional hazards regressionCompare patient outcomesProportional hazards regressionIII melanomaImmunotherapy receiptReceiving immunotherapyIII diseaseImmunotherapy agentsOverall survivalSurvival benefitAdjuvant treatment
2023
830 Inhibition of macrophage migration inhibitory factor (MIF) to overcome immune checkpoint resistance in melanoma
Sanchez-Zuno G, Caulfield J, Leng L, Zhang L, Jilaveanu L, Kluger H, Bucala R, Tran T. 830 Inhibition of macrophage migration inhibitory factor (MIF) to overcome immune checkpoint resistance in melanoma. 2023, a928-a928. DOI: 10.1136/jitc-2023-sitc2023.0830.Peer-Reviewed Original ResearchThe SNP rs755622 is associated with immune activation in glioblastoma
Alban T, Grabowski M, Otvos B, Bayik D, Wang W, Zalavadia A, Makarav V, Troike K, McGraw M, Rabljenovic A, Lauko A, Neumann C, Roversi G, Waite K, Cioffi G, Patil N, Tran T, McCortney K, Steffens A, Diaz-Montero C, Brown J, Egan K, Horbinski C, Barnholtz-Sloan J, Rajappa P, Vogelbaum M, Bucala R, Chan T, Ahluwalia M, Lathia J. The SNP rs755622 is associated with immune activation in glioblastoma. JCI Insight 2023, 8: e160024. PMID: 37252795, PMCID: PMC10371339, DOI: 10.1172/jci.insight.160024.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImmune activationCytokine macrophage migration inhibitory factorMigration inhibitory factorLactotransferrin (LTF) expressionLeukocyte infiltrationHallmark of glioblastomaImmune microenvironmentTreatment responseRs755622Inhibitory factorDrug resistanceGermline mutationsIntratumoral heterogeneityTumoral microenvironmentGermline SNPsGlioblastomaLenvatinib 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 modelFactors associated with the use of adjuvant radiation therapy in stage III melanoma
King A, Lee V, Yu B, Mirza F, Zogg C, Yang D, Tran T, Leventhal J, An Y. Factors associated with the use of adjuvant radiation therapy in stage III melanoma. Frontiers In Oncology 2023, 13: 1005930. PMID: 36816935, PMCID: PMC9929351, DOI: 10.3389/fonc.2023.1005930.Peer-Reviewed Original ResearchAdjuvant radiation therapyStage III melanomaNational Cancer Data BaseRadiation therapyPositive nodesNational Comprehensive Cancer Network guidelinesUse of RTUtilization of RTMultivariable logistic regression analysisPalliative intent therapyDistant metastatic diseasePrimary treatment modalityMajority of patientsMicroscopic residual tumorHospital-specific factorsMultivariable regression analysisLogistic regression analysisRegression analysisMetastatic diseaseOverall cohortResidual tumorDisease benefitNetwork guidelinesPalliative careMean ageCurrent diagnosis and management of cardiac melanoma: a case series and review
Long A, Chang J, Glahn J, Olino K, Tran T, Clune J. Current diagnosis and management of cardiac melanoma: a case series and review. Journal Of Cancer Metastasis And Treatment 2023, 9: null-null. DOI: 10.20517/2394-4722.2022.113.Peer-Reviewed Original ResearchUse of immunotherapyCardiac melanomaCardiac tumorsSurveillance imagingMalignant melanomaRoutine surveillance imagingCardiac metastasisCase seriesCDKN2A variantsClinical findingsAutopsy studyBRAF mutationsNRAS mutationsPatientsCurrent diagnosisImmunotherapyMelanomaGenetic profilingHigh rateTumorsDiagnosisImagingMetastasisTherapySymptoms
2021
Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells
Tran TT, Rane CK, Zito CR, Weiss SA, Jessel S, Lucca L, Lu BY, Oria VO, Adeniran A, Chiang VL, Omay SB, Hafler DA, Kluger HM, Jilaveanu LB. Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers 2021, 13: 1049. PMID: 33801444, PMCID: PMC7958624, DOI: 10.3390/cancers13051049.Peer-Reviewed Original ResearchPDCD4 expressionImproved survivalTumor-Associated Immune CellsTumor microenvironmentNeoplastic progressionBrain metastasis outcomesExtracranial metastatic diseaseMelanoma brain metastasesNatural killer cellsBrain metastasis samplesImmune cell infiltrationImmune cell subsetsMultiple tissue microarraysExpression of PDCD4Brain metastasesMetastatic diseaseClinical outcomesKiller cellsClinicopathological variablesIntracranial metastasesCell subsetsCell infiltrationCell death 4Immune cellsPrimary melanoma
2020
Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trialsElective Colectomy in a Patient with Active Ulcerative Colitis and Metastatic Melanoma Enabling Successful Treatment with Immune Checkpoint Inhibitors.
Perdigoto AL, Tran T, Patel N, Clark P, Patell K, Stamatouli AM, Reddy V, Clune J, Herold KC, Robert ME, Kluger HM. Elective Colectomy in a Patient with Active Ulcerative Colitis and Metastatic Melanoma Enabling Successful Treatment with Immune Checkpoint Inhibitors. Clinical Oncology Case Reports 2020, 3 PMID: 33778814, PMCID: PMC7993656.Peer-Reviewed Original ResearchCheckpoint inhibitor therapyElective colectomyUlcerative colitisInhibitor therapyMetastatic melanomaImmune-related adverse eventsExcellent tumor responseImmune checkpoint inhibitorsSevere ulcerative colitisActive ulcerative colitisCheckpoint inhibitor immunotherapyCheckpoint inhibitor treatmentInflammatory bowel diseaseEffective treatment optionBenefits of treatmentImmune system activationTumor cell destructionCheckpoint inhibitorsAdvanced malignanciesAdverse eventsSelect patientsBowel diseaseAutoimmune diseasesTreatment optionsTumor response19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA
Oria V, Zhang H, Zhu H, Deng G, Zito C, Rane C, Zhang S, Weiss S, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg M, Kluger H, Jilaveanu L. 19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA. Neuro-Oncology Advances 2020, 2: ii3-ii3. PMCID: PMC7401364, DOI: 10.1093/noajnl/vdaa073.009.Peer-Reviewed Original ResearchMelanoma brain metastasesBrain metastasesTumor growthPI3K/Akt/mTORCell cycle transitionAkt/mTORGrowth of tumorsS cell cycle transitionPhosphorylation of AktMelanoma patientsPoor prognosisNovel drug targetsPatient populationRegulation of PDCD4Metastatic melanomaUnique cohortXenograft modelClinical relevanceNude miceMetastasisCycle transitionMelanomaBrain developmentKey mediatorMelanoma cellsPembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial
Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Wilson FH, Omay SB, Yu JB, Jilaveanu L, Tran T, Pavlik K, Rowen E, Gerrish H, Komlo A, Gupta R, Wyatt H, Ribeiro M, Kluger Y, Zhou G, Wei W, Chiang VL, Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2020, 21: 655-663. PMID: 32251621, PMCID: PMC7380514, DOI: 10.1016/s1470-2045(20)30111-x.Peer-Reviewed Original ResearchConceptsBrain metastasis responseYale Cancer CenterPD-L1 expressionPhase 2 trialUntreated brain metastasesBrain metastasesAdrenal insufficiencyAdverse eventsMetastasis responseCNS diseaseCancer CenterCohort 2Cohort 1Eastern Cooperative Oncology Group performance statusTreatment-related serious adverse eventsModified Response Evaluation CriteriaStage IV NSCLCTreatment-related deathsAcute kidney injuryPD-1 blockadeSerious adverse eventsSolid Tumors criteriaPhase 2 studyProportion of patientsResponse Evaluation Criteria