2024
High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC)
Moutafi M, Bates K, Aung T, Milian R, Xirou V, Vathiotis I, Gavrielatou N, Angelakis A, Schalper K, Salichos L, Rimm D. High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2024, 12: e009039. PMID: 38857914, PMCID: PMC11168162, DOI: 10.1136/jitc-2024-009039.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsProgrammed cell death protein 1Associated with OSCell lung cancerTissue microarray spotsTissue microarrayValidation cohortLung cancerNon-small cell lung cancer treated with immune checkpoint inhibitorsAssociated with resistance to immunotherapyCell death protein 1Resistance to immunotherapyAssociated with PFSProgression-free survivalSecreted frizzled-related protein 2Cox proportional-hazards model analysisCheckpoint inhibitorsImmunotherapy strategiesTumor compartmentsRetrospective cohortDiscovery cohortLong-term benefitsPatientsCD68
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 ResearchMeSH KeywordsB7-H1 AntigenHumansImmune Checkpoint InhibitorsIpilimumabMelanomaNivolumabTumor MicroenvironmentConceptsImmune 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 patternsDigital 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 ResearchMeSH KeywordsCarcinomaHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckConceptsDigital 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 survivalAn Algorithm as a Biomarker for Response to Immune Checkpoint Inhibitor Therapy
Rimm D. An Algorithm as a Biomarker for Response to Immune Checkpoint Inhibitor Therapy. JAMA Oncology 2023, 9: 60-61. PMID: 36394848, DOI: 10.1001/jamaoncol.2022.4772.Peer-Reviewed Original Research
2022
Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit.
Hayes D, Herbst R, Myles J, Topalian S, Yohe S, Aronson N, Bellizzi A, Basu Roy U, Bradshaw G, Edwards R, El-Gabry E, Elvin J, Gajewski T, McShane L, Oberley M, Philip R, Rimm D, Rosenbaum J, Rubin E, Schlager L, Sherwood S, Stewart M, Taube J, Thurin M, Vasalos P, Laser J. Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit. JCO Precision Oncology 2022, 6: e2200454. PMID: 36446042, PMCID: PMC10530621, DOI: 10.1200/po.22.00454.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkers, TumorHumansImmune Checkpoint InhibitorsMedicareMicrosatellite InstabilityNeoplasmsPathologistsUnited StatesConceptsICI therapyImmune checkpoint inhibition therapyDeath ligand 1 (PD-L1) expressionMultiple predictive biomarkersTumor biomarker testsCheckpoint inhibition therapyLigand 1 expressionDeath ligand 1Field of oncologyICI benefitPredictive factorsPredictive biomarkersInhibition therapyNeoantigen expressionBiomarker testsHealth insurance organizationsUS FoodDrug AdministrationAmerican PathologistsMedicaid ServicesTherapyBiomarker developmentNational InstituteLigand 1Clinical applicationInhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansImmune Checkpoint InhibitorsImmunotherapyMelanomaMiceMonoamine OxidaseTumor MicroenvironmentConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatment
2021
Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC
Doroshow DB, Wei W, Gupta S, Zugazagoitia J, Robbins C, Adamson B, Rimm DL. Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC. Journal Of Thoracic Oncology 2021, 16: 2139-2143. PMID: 34455068, PMCID: PMC8612948, DOI: 10.1016/j.jtho.2021.07.032.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreHigh PD-L1 tumor proportion scoreOverall survivalNonsquamous histologySquamous NSCLCNonsquamous NSCLCPredictive biomarkersProportion scoreDeath ligand 1 (PD-L1) tumor proportion scoreElectronic health record-derived databaseFirst-line pembrolizumab therapyPD-1 expression levelsPD-L1 expression levelsCommunity oncology clinicsMedian OS differenceSingle-agent pembrolizumabImmune checkpoint inhibitorsImproved overall survivalMedian overall survivalPrimary end pointFirst-line pembrolizumabFirst-line therapyPD-L1 expressionPD-L1 testingPD-L1 as a biomarker of response to immune-checkpoint inhibitors
Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS, Hirsch FR. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nature Reviews Clinical Oncology 2021, 18: 345-362. PMID: 33580222, DOI: 10.1038/s41571-021-00473-5.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, PharmacologicalBiomarkers, TumorBiopsyHumansImmune Checkpoint InhibitorsImmunohistochemistryNeoplasmsSpecimen HandlingTreatment OutcomeConceptsImmune checkpoint inhibitorsSelection of patientsPD-L1L1 antibodyImmunohistochemistry assaysPD-L1 immunohistochemistry assaysOutcomes of patientsBiomarkers of responseCompanion diagnostic assayTypes of cancerPD-1Clinical outcomesSelection biomarkerProspective comparisonClinical challengeNew therapiesFuture treatmentPatientsSolid tumorsClinical useSpecific agentsInter-assay variabilityBiomarkersCurrent roleDiagnostic assaysBiomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry
Martinez-Morilla S, Villarroel-Espindola F, Wong PF, Toki MI, Aung TN, Pelekanou V, Bourke-Martin B, Schalper KA, Kluger HM, Rimm DL. Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry. Clinical Cancer Research 2021, 27: 1987-1996. PMID: 33504554, PMCID: PMC8026677, DOI: 10.1158/1078-0432.ccr-20-3340.Peer-Reviewed Original ResearchMeSH KeywordsBeta 2-MicroglobulinBiomarkers, TumorHumansImage CytometryImmune Checkpoint InhibitorsMelanomaRNA, MessengerTissue Array AnalysisTumor MicroenvironmentUsing Machine Learning Algorithms to Predict Immunotherapy Response in Patients with Advanced Melanoma
Johannet P, Coudray N, Donnelly DM, Jour G, Illa-Bochaca I, Xia Y, Johnson DB, Wheless L, Patrinely JR, Nomikou S, Rimm DL, Pavlick AC, Weber JS, Zhong J, Tsirigos A, Osman I. Using Machine Learning Algorithms to Predict Immunotherapy Response in Patients with Advanced Melanoma. Clinical Cancer Research 2021, 27: 131-140. PMID: 33208341, PMCID: PMC7785656, DOI: 10.1158/1078-0432.ccr-20-2415.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDisease ProgressionDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedImmune Checkpoint InhibitorsMachine LearningMaleMelanomaMiddle AgedNeoplasm StagingPrognosisProgression-Free SurvivalProspective StudiesRisk AssessmentROC CurveSkinSkin NeoplasmsConceptsProgression-free survivalImmune checkpoint inhibitorsLower riskClinicodemographic characteristicsAdvanced melanomaClinical dataWorse progression-free survivalICI treatment outcomesKaplan-Meier curvesBiomarkers of responseStandard of careCheckpoint inhibitorsICI responseImmunotherapy responseValidation cohortTraining cohortDisease progressionProspective validationTreatment outcomesHigh riskClinical practicePatientsROC curveProgressionRisk
2020
Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling
Zugazagoitia J, Gupta S, Liu Y, Fuhrman K, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling. Clinical Cancer Research 2020, 26: 4360-4368. PMID: 32253229, PMCID: PMC7442721, DOI: 10.1158/1078-0432.ccr-20-0175.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-1 checkpoint blockadeCell lung cancerCheckpoint blockadeLung cancerAdvanced non-small cell lung cancerUnivariate unadjusted analysisProgression-free survivalImmune cell countsMinority of patientsRobust predictive biomarkersBiomarkers of responseLarge independent cohortsSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyOverall survivalClinical outcomesImmune predictorsHigher CD56NSCLC casesPredictive biomarkersUnadjusted analysesImmune parametersTissue microarray