2024
Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung T, Warrell J, Martinez-Morilla S, Gavrielatou N, Vathiotis I, Yaghoobi V, Kluger H, Gerstein M, Rimm D. Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma. Clinical Cancer Research 2024, 30: 3520-3532. PMID: 38837895, PMCID: PMC11326985, DOI: 10.1158/1078-0432.ccr-23-3932.Peer-Reviewed Original ResearchGene signatureResistance to immunotherapyResponse to immunotherapyPrediction of treatment outcomeResistant to treatmentAccurate prediction of treatment outcomePredictive of responseImmunotherapy outcomesMelanoma patientsMelanoma specimensValidation cohortPatient stratificationDiscovery cohortTreatment outcomesImmunotherapyMelanomaTumorPatientsCohortS100BOutcomesGene expression dataGenesCD68+macrophagesExpression data
2023
Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy
Martinez-Morilla S, Moutafi M, Fernandez A, Jessel S, Divakar P, Wong P, Garcia-Milian R, Schalper K, Kluger H, Rimm D. Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy. OncoImmunology 2023, 12: 2260618. PMID: 37781235, PMCID: PMC10540659, DOI: 10.1080/2162402x.2023.2260618.Peer-Reviewed Original ResearchConceptsDigital spatial profilingImmune checkpoint inhibitor therapyShorter progression-free survivalQuantitative immunofluorescenceCheckpoint inhibitor therapyProgression-free survivalMetastatic melanoma patientsPre-treatment specimensIndependent validation cohortMetastatic melanoma casesAdjuvant settingNanoString GeoMxMultivariable adjustmentAdverse eventsImmunotherapy cohortInhibitor therapyPD-L1Immune markersMelanoma patientsUnivariable analysisValidation cohortImmune cellsMelanoma casesMultiplex immunofluorescenceCD95 expressionDeterminants of overall survival in patients with metastatic uveal melanoma
Demkowicz P, Pointdujour‐Lim R, Miguez S, Lee Y, Jones B, Barker C, Bosenberg M, Abramson D, Shoushtari A, Kluger H, Francis J, Sznol M, Bakhoum M. Determinants of overall survival in patients with metastatic uveal melanoma. Cancer 2023, 129: 3275-3286. PMID: 37382208, PMCID: PMC11149607, DOI: 10.1002/cncr.34927.Peer-Reviewed Original ResearchConceptsAnti-PD-1 therapyMetastatic uveal melanomaDeath hazard ratioImmune checkpoint inhibitorsOverall survivalHazard ratioUveal melanomaSurvival outcomesFemale sexCheckpoint inhibitorsECOG scoreValidation cohortEastern Cooperative Oncology Group performance status scaleGood baseline performance statusMetastatic uveal melanoma patientsMetastatic UM patientsImproved overall survivalMedian overall survivalBaseline performance statusBetter survival outcomesImproved survival outcomesPotential of immunotherapyWorse survival outcomesImmune checkpoint therapyKaplan-Meier analysisSubsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patterns
2021
Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
Moore MR, Friesner ID, Rizk EM, Fullerton BT, Mondal M, Trager MH, Mendelson K, Chikeka I, Kurc T, Gupta R, Rohr BR, Robinson EJ, Acs B, Chang R, Kluger H, Taback B, Geskin LJ, Horst B, Gardner K, Niedt G, Celebi JT, Gartrell-Corrado RD, Messina J, Ferringer T, Rimm DL, Saltz J, Wang J, Vanguri R, Saenger YM. Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma. Scientific Reports 2021, 11: 2809. PMID: 33531581, PMCID: PMC7854647, DOI: 10.1038/s41598-021-82305-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiopsyChemotherapy, AdjuvantClinical Decision-MakingDeep LearningFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNeoplasm StagingPatient SelectionPrognosisRetrospective StudiesRisk AssessmentROC CurveSkinSkin NeoplasmsYoung AdultConceptsTumor-infiltrating lymphocytesDisease-specific survivalEarly-stage melanomaOpen-source deep learningCutoff valueMultivariable Cox proportional hazards analysisCox proportional hazards analysisDeep learningLow-risk patientsProportional hazards analysisKaplan-Meier analysisAccurate prognostic biomarkersEosin imagesAccuracy of predictionAdjuvant therapyRisk patientsSpecific survivalPrognostic valueValidation cohortReceiver operating curvesTraining cohortTIL analysisClinical trialsPrimary melanomaPrognostic biomarker
2018
A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma
Weber JS, Sznol M, Sullivan RJ, Blackmon S, Boland G, Kluger HM, Halaban R, Bacchiocchi A, Ascierto PA, Capone M, Oliveira C, Meyer K, Grigorieva J, Asmellash SG, Roder J, Roder H. A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma. Cancer Immunology Research 2018, 6: 79-86. PMID: 29208646, DOI: 10.1158/2326-6066.cir-17-0412.Peer-Reviewed Original ResearchConceptsAcute phase reactantsCheckpoint inhibitorsOverall survivalPhase reactantsIpilimumab-treated patientsPD-1 blockadeTrials of nivolumabBetter overall survivalIndependent patient cohortsPretreatment serumPD-1Melanoma patientsValidation cohortMetastatic melanomaMultipeptide vaccinePatient cohortPooled analysisWorse outcomesClinical dataPatientsMultivariate analysisComplement cascadeMass spectrometry analysisNivolumabCohort