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 links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survival
2022
Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade
Vathiotis I, Salichos L, Martinez-Morilla S, Gavrielatou N, Aung T, Shafi S, Wong P, Jessel S, Kluger H, Syrigos K, Warren S, Gerstein M, Rimm D. Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade. Npj Precision Oncology 2022, 6: 92. PMID: 36522538, PMCID: PMC9755314, DOI: 10.1038/s41698-022-00330-3.Peer-Reviewed Original ResearchProgression-free survivalLong-term benefitsPredictive valueAnti-PD-1 therapyCell death protein 1Baseline tumor samplesImmune checkpoint inhibitorsAntitumor immune responseCohort of patientsDeath protein 1Gene expression profilesAdvanced diseaseCheckpoint inhibitorsAdvanced melanomaAxis blockadeImmunotherapy outcomesTreatment initiationEarly outcomesDisease progressionMalignant melanomaBaseline gene expressionImmune responseBaseline gene expression profilesExpression profilesTumor samplesAssociation of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer
Gavrielatou N, Liu Y, Vathiotis I, Zugazagoitia J, Aung TN, Shafi S, Fernandez A, Schalper K, Psyrri A, Rimm DL. Association of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer. Clinical Cancer Research 2022, 28: clincanres.2649.2021. PMID: 34686497, PMCID: PMC8776595, DOI: 10.1158/1078-0432.ccr-21-2649.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerBest overall responsePD-L1 tumor proportion scorePD-1/PD-L1Immune checkpoint inhibitorsProgression-free survivalTumor proportion scoreCell lung cancerPD-L1Immunotherapy outcomesCheckpoint inhibitorsOverall survivalQuantitative immunofluorescenceLung cancerProportion scoreAdvanced non-small cell lung cancerLocal T cell responsesCell death protein 1Immunotherapy-treated patientsMultiplexed quantitative immunofluorescencePD-1 expressionPD-L1 expressionDeath protein 1Selection of patientsT cell responses
2019
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomesClosed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma
Gupta S, McCann L, Chan YGY, Lai EW, Wei W, Wong PF, Smithy JW, Weidler J, Rhees B, Bates M, Kluger HM, Rimm DL. Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 254. PMID: 31533832, PMCID: PMC6751819, DOI: 10.1186/s40425-019-0731-9.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD8 AntigensFemaleFollow-Up StudiesGene Expression ProfilingHumansInterferon Regulatory Factor-1MaleMelanomaMiddle AgedMonitoring, ImmunologicPrognosisProgrammed Cell Death 1 Ligand 2 ProteinProgression-Free SurvivalReal-Time Polymerase Chain ReactionRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSkin NeoplasmsConceptsCompanion diagnostic testsImmunotherapy outcomesMelanoma patientsClinical benefitAnti-PD-1 therapyImmune checkpoint inhibitor therapyMRNA expressionQuantitative immunofluorescenceDiagnostic testsCheckpoint inhibitor therapyReal-time quantitative reverse transcription polymerase chain reactionMetastatic melanoma patientsQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionYale Pathology archivesParaffin-embedded tissue sectionsAdjuvant settingICI therapyOS associationInhibitor therapyBaseline variablesMetastatic melanomaPredictive biomarkersPolymerase chain reactionMultiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma
Wong PF, Wei W, Gupta S, Smithy JW, Zelterman D, Kluger HM, Rimm DL. Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 194. PMID: 31337426, PMCID: PMC6651990, DOI: 10.1186/s40425-019-0675-0.Peer-Reviewed Original ResearchConceptsProgression-free survivalBest overall responseSmooth muscle actinOverall survivalCell countQuantitative immunofluorescenceImmune markersImmunotherapy outcomesMelanoma patientsSignificant progression-free survivalAnti-PD-1 therapyAbsence of immunotherapyPretreatment tumor specimensImmune checkpoint blockadeCell death 1Cancer-associated fibroblast (CAF) populationNegative prognostic biomarkerCancer-associated fibroblastsWhole tissue sectionsOverall responseOS associationCAF parametersCheckpoint blockadeImmune dysregulationDeath-1Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman K, Zelterman D, Kluger HM, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma. Clinical Cancer Research 2019, 25: 2442-2449. PMID: 30617133, PMCID: PMC6467753, DOI: 10.1158/1078-0432.ccr-18-2652.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkersBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingROC CurveT-Lymphocyte SubsetsConceptsCell countTIL activationQuantitative immunofluorescenceLymphocytic infiltrationMelanoma patientsMetastatic melanomaAnti-PD-1 responseAnti-PD-1 therapyCell death 1 (PD-1) inhibitionAbsence of immunotherapyDeath-1 (PD-1) inhibitionDisease control rateProgression-free survivalCD8 cell countsTumor-Infiltrating LymphocytesNew predictive biomarkersWhole tissue sectionsRECIST 1.1Progressive diseaseDurable responsesObjective responsePartial responseImmunotherapy outcomesLymphocyte profilesMultivariable analysis