2023
Subsets 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
2020
Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges.
McKean WB, Moser JC, Rimm D, Hu-Lieskovan S. Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges. American Society Of Clinical Oncology Educational Book 2020, 40: e275-e291. PMID: 32453632, DOI: 10.1200/edbk_280571.Peer-Reviewed Original ResearchConceptsHost immune defectsPrecision cancer immunotherapyHealth care burdenCurrent treatment modalitiesSignificant side effectsSustained remissionClinical responseCheckpoint inhibitionImmune defectsRefractory malignanciesCancer immunotherapeuticsClinical benefitPatient survivalCancer immunotherapyPredictive biomarkersTreatment modalitiesCare burdenPatient responseSide effectsTrial designTumor parenchymaClinical useBiomarker developmentBiomarkersMultiple biomarkers
2018
Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma
Johnson DB, Bordeaux J, Kim J, Vaupel C, Rimm DL, Ho TH, Joseph RW, Daud AI, Conry RM, Gaughan EM, Hernandez-Aya LF, Dimou A, Funchain P, Smithy J, Witte JS, McKee SB, Ko J, Wrangle J, Dabbas B, Tangri S, Lameh J, Hall J, Markowitz J, Balko JM, Dakappagari N. Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma. Clinical Cancer Research 2018, 24: 5250-5260. PMID: 30021908, PMCID: PMC6214750, DOI: 10.1158/1078-0432.ccr-18-0309.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyCell Line, TumorFemaleHLA-DR AntigensHumansImmunohistochemistryIndoleamine-Pyrrole 2,3,-DioxygenaseMaleMelanomaMiddle AgedModels, BiologicalNeoplasm MetastasisNeoplasm StagingPrognosisProgrammed Cell Death 1 ReceptorProtein BindingRetreatmentTreatment OutcomeConceptsAnti-PD-1 responseHLA-DRValidation cohortPD-1/PD-L1PD-1 blockersPD-1 monotherapyPD-L1 expressionPretreatment tumor biopsiesProgression-free survivalSubset of patientsAcademic cancer centerBiomarkers of responseIndependent validation cohortClin Cancer ResImmunosuppression mechanismsClinical responseOverall survivalPD-L1Melanoma patientsCancer CenterTreatment outcomesTumor biopsiesDiscovery cohortPatientsIndividual biomarkersExceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic options
2017
Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers.
Datar I, Mani N, Henick B, Wurtz A, Kaftan E, Herbst R, Rimm D, Gettinger S, Politi K, Schalper K. Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers. Journal Of Clinical Oncology 2017, 35: e14611-e14611. DOI: 10.1200/jco.2017.35.15_suppl.e14611.Peer-Reviewed Original ResearchNon-small cell lung carcinomaTim-3PD-1LAG-3T cellsInhibitory receptorsAdvanced non-small cell lung carcinomaPD-1 axis blockadeHigh TIM-3Immune suppressive pathwaysImmune inhibitory receptorsCell lung carcinomaMembranous staining patternPre-treatment samplesWhole tissue sectionsWhole tumor areaClinical responseMost patientsAxis blockadeLow levelsLung carcinomaT lymphocytesMultiplex immunofluorescenceHigh levelsSuppressive pathways
2014
Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib
Wilson MA, Zhao F, Letrero R, D'Andrea K, Rimm DL, Kirkwood JM, Kluger HM, Lee SJ, Schuchter LM, Flaherty KT, Nathanson KL. Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib. Clinical Cancer Research 2014, 20: 3328-3337. PMID: 24714776, PMCID: PMC4058354, DOI: 10.1158/1078-0432.ccr-14-0093.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinDouble-Blind MethodFemaleFollow-Up StudiesGenotypeGTP PhosphohydrolasesHumansMaleMelanomaMembrane ProteinsMiddle AgedMutationNeoplasm StagingNiacinamidePaclitaxelPhenylurea CompoundsPrognosisProto-Oncogene Proteins B-rafSkin NeoplasmsSorafenibSurvival RateConceptsProgression-free survivalNRAS-mutant melanomaPlatelet-derived growth factor receptorPerformance statusClinical outcomesNRAS mutationsCox proportional hazards modelVEGF receptorsSomatic mutationsWorse performance statusGood performance statusImproved clinical responseKaplan-Meier methodClinical trial populationsPretreatment tumor samplesSite of diseaseProportional hazards modelEffect of sorafenibBRAF-mutant melanomaFisher's exact testGrowth factor receptorClinical responseOverall survivalClinicopathologic featuresMelanoma patients