Featured Publications
Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test
Fernandez A, Gaule P, Rimm D. Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test. Modern Pathology 2023, 36: 100159. PMID: 36925070, PMCID: PMC10502188, DOI: 10.1016/j.modpat.2023.100159.Peer-Reviewed Original ResearchConceptsPD-L1 signalTumor proportion scoreTissue microarray cohortCell lung cancerPrevious clinical diagnosisWhole tissue sectionsCompanion diagnostic testsMultiple cancer typesMicroarray cohortTMA cohortLaboratory-developed testsPD-L1NSCLC casesLung cancerProportion scorePositive stainingAntibody 22C3Immunohistochemistry testsClinical diagnosisExtracellular domainCancer typesDiagnostic testsArchival tissueDomain antigenAntibodies
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
Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitorsQuantitative, Spatially Defined Expression of Leukocyte Associated Immunoglobulin-like Receptor (LAIR-1) in Non-Small Cell Lung Cancer
Aung T, Gavrielatou N, Vathiotis I, Fernandez A, Shafi S, Yaghoobi V, Burela S, MacNeil T, Ahmed F, Myint H, Flies D, Langermann S, Rimm D. Quantitative, Spatially Defined Expression of Leukocyte Associated Immunoglobulin-like Receptor (LAIR-1) in Non-Small Cell Lung Cancer. Cancer Research Communications 2023, 3: 471-482. PMID: 36960400, PMCID: PMC10029762, DOI: 10.1158/2767-9764.crc-22-0334.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunoglobulinsLeukocytesLung NeoplasmsConceptsNon-small cell lung cancerLeukocyte-associated immunoglobulin-like receptor-1LAIR-1 expressionMultiplexed quantitative immunofluorescenceCell lung cancerLung adenocarcinomaLung cancerPD-L1Anti-PD-1/PD-L1Anti-PD-1 resistanceSquamous cell carcinoma subtypeImmunoglobulin-like receptor-1Cancer immunotherapeutic strategiesDeath-1 blockadeResistant lung tumorsImmunoglobulin-like receptorsCell typesAntitumor immunityImmunotherapeutic strategiesHistologic subtypePrognostic valueCombination therapyLung tumorsCarcinoma subtypesLAIR-2Spatial characterization and quantification of CD40 expression across cancer types
Bates K, Vathiotis I, MacNeil T, Ahmed F, Aung T, Katlinskaya Y, Bhattacharya S, Psyrri A, Yea S, Parkes A, Sadraei N, Roychoudhury S, Rimm D, Gavrielatou N. Spatial characterization and quantification of CD40 expression across cancer types. BMC Cancer 2023, 23: 220. PMID: 36894898, PMCID: PMC9996913, DOI: 10.1186/s12885-023-10650-7.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Non-Small-Cell LungCD40 AntigensFemaleHumansLung NeoplasmsOvarian NeoplasmsPancreatic NeoplasmsConceptsCD40 expressionSolid tumorsTumor cellsQuantitative immunofluorescencePatient cohortPancreatic cancerCancer typesExpression of CD40Large patient cohortOvarian cancer populationTissue microarray formatDifferent solid tumorsInnate immune responseTNF receptor family membersAvailable patient cohortNSCLC populationOverall survivalPrognostic impactReceptor family membersCancer populationAdenocarcinoma populationImmune cellsOvarian cancerPancreatic adenocarcinomaPositivity rate
2022
Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordanceAssociation 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
2021
Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma
Fisk JN, Mahal AR, Dornburg A, Gaffney SG, Aneja S, Contessa JN, Rimm D, Yu JB, Townsend JP. Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma. Cancer Letters 2021, 526: 346-351. PMID: 34780851, PMCID: PMC8702484, DOI: 10.1016/j.canlet.2021.11.011.Peer-Reviewed Original ResearchConceptsMutational processesSingle ancestral lineageAncestral lineageProgression of cancerMetastatic lineagesPhylogenetic analysisGenetic resistanceEvolutionary processesExogenous mutational processesCancer evolutionConsolidative therapyMutational signature analysisEGFR-positive non-small cell lung cancerNon-small cell lung cancerKey eventsLineagesCell populationsTherapeutic resistanceLocal consolidative therapyClinical time courseCell lung cancerDisease etiologyTherapeutic decision makingCisplatin therapyLung cancerStandardization of PD-L1 immunohistochemistry
Martinez-Morilla S, Moutafi M, Rimm DL. Standardization of PD-L1 immunohistochemistry. Modern Pathology 2021, 35: 294-295. PMID: 34508229, PMCID: PMC8860739, DOI: 10.1038/s41379-021-00917-4.Peer-Reviewed Original ResearchProgrammed 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 Expression Scoring: Noninterchangeable, Noninterpretable, Neither, or Both
Gavrielatou N, Shafi S, Gaule P, Rimm DL. PD-L1 Expression Scoring: Noninterchangeable, Noninterpretable, Neither, or Both. Journal Of The National Cancer Institute 2021, 113: 1613-1614. PMID: 34097056, PMCID: PMC8634453, DOI: 10.1093/jnci/djab109.Peer-Reviewed Original ResearchComparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer
Moutafi MK, Tao W, Huang R, Haberberger J, Alexander B, Ramkissoon S, Ross JS, Syrigos K, Wei W, Pusztai L, Rimm DL, Vathiotis IA. Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: e002230. PMID: 33833050, PMCID: PMC8039214, DOI: 10.1136/jitc-2020-002230.Peer-Reviewed Original ResearchConceptsPD-L1 expressionMetastatic lesionsLung cancer casesLung cancerCancer casesAdvanced stage non-small cell lung cancerNon-small cell lung cancerNon-squamous histologyCell lung cancerFuture patient managementDefinite diagnostic testSquamous histologyFoundation MedicineLymph nodesRoutine careHistologic subtypeMetastatic sitesPrimary lesionRetrospective studyAdrenal glandPrimary tumorPleural fluidPatient managementTrial designDrug AdministrationSpatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
Datar IJ, Hauc SC, Desai S, Gianino N, Henick B, Liu Y, Syrigos K, Rimm DL, Kavathas P, Ferrone S, Schalper KA. Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer. Clinical Cancer Research 2021, 27: 2837-2847. PMID: 33602682, PMCID: PMC8734284, DOI: 10.1158/1078-0432.ccr-20-3655.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerNK cell infiltrationReduced T cellCell lung cancerHLA class IIT cellsLung cancerHLA classClinical significanceSubunit expressionHLA class II downregulationΒ2MClass IIHLA genesHuman leukocyte antigen classShorter overall survivalTumor microenvironment compositionClass II β chainImmune contextureOverall survivalLung malignancyNatural killerPatient survivalCell infiltrationClinicopathologic variables
2020
Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapy
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 outcomesImmunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes
Doroshow DB, Sanmamed MF, Hastings K, Politi K, Rimm DL, Chen L, Melero I, Schalper KA, Herbst RS. Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes. Clinical Cancer Research 2019, 25: 4592-4602. PMID: 30824587, PMCID: PMC6679805, DOI: 10.1158/1078-0432.ccr-18-1538.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCell lung cancerPD-L1Lung cancerNonsquamous non-small cell lung cancerOngoing translational workPD-1 axisFirst-line therapyPD-L1 expressionProportion of patientsTumor mutational burdenAdvanced diseaseOverall survivalTumor inflammationMutational burdenPatientsNovel markerChemotherapyTherapyIndicative biomarkersCancerTranslational workBiomarkersSurvivalExpression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis
Datar I, Sanmamed MF, Wang J, Henick BS, Choi J, Badri T, Dong W, Mani N, Toki M, Mejías L, Lozano MD, Perez-Gracia JL, Velcheti V, Hellmann MD, Gainor JF, McEachern K, Jenkins D, Syrigos K, Politi K, Gettinger S, Rimm DL, Herbst RS, Melero I, Chen L, Schalper KA. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis. Clinical Cancer Research 2019, 25: 4663-4673. PMID: 31053602, PMCID: PMC7444693, DOI: 10.1158/1078-0432.ccr-18-4142.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDBiomarkers, TumorCarcinoma, Non-Small-Cell LungGene Expression Regulation, NeoplasticHepatitis A Virus Cellular Receptor 2HumansLung NeoplasmsLymphocyte ActivationLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingPrognosisProgrammed Cell Death 1 ReceptorRetrospective StudiesSingle-Cell AnalysisSurvival RateConceptsNon-small cell lung cancerHuman non-small cell lung cancerTumor-infiltrating lymphocytesAdvanced non-small cell lung cancerTim-3PD-1Cell lung cancerLAG-3Lung cancerPD-1 axis blockadeShorter progression-free survivalBaseline samplesTim-3 protein expressionMajor clinicopathologic variablesMultiplexed quantitative immunofluorescencePD-1 expressionProgression-free survivalTim-3 expressionLAG-3 expressionT-cell phenotypeTumor mutational burdenImmune inhibitory receptorsImmune evasion pathwaysTIM-3 proteinMass cytometry analysisA Multi-Institutional Study to Evaluate Automated Whole Slide Scoring of Immunohistochemistry for Assessment of Programmed Death-Ligand 1 (PD-L1) Expression in Non–Small Cell Lung Cancer
Taylor CR, Jadhav AP, Gholap A, Kamble G, Huang J, Gown A, Doshi I, Rimm DL. A Multi-Institutional Study to Evaluate Automated Whole Slide Scoring of Immunohistochemistry for Assessment of Programmed Death-Ligand 1 (PD-L1) Expression in Non–Small Cell Lung Cancer. Applied Immunohistochemistry & Molecular Morphology 2019, 27: 263-269. PMID: 30640753, DOI: 10.1097/pai.0000000000000737.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerImmune cellsTumor cellsLin's concordance correlation coefficientLung cancerProgrammed Death Ligand 1 ExpressionDako Link 48 platformDeath ligand 1 (PD-L1) expressionNon-small cell lung carcinomaPD-L1 expressionPD-L1 immunohistochemistryImmune cell populationsImmune cell expressionCell lung carcinomaCell scoringMulti-institutional studyConcordance correlation coefficientImage analysis scoresPD-L1Cell positivityLung carcinomaPatient managementSlide scoringCell expressionExpression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC)
Carvajal-Hausdorf D, Altan M, Velcheti V, Gettinger SN, Herbst RS, Rimm DL, Schalper KA. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC). Journal For ImmunoTherapy Of Cancer 2019, 7: 65. PMID: 30850021, PMCID: PMC6408760, DOI: 10.1186/s40425-019-0540-1.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overB7 AntigensB7-H1 AntigenBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm GradingNeoplasm StagingPrognosisRetrospective StudiesSmall Cell Lung CarcinomaV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsSmall cell lung cancerCell lung cancerB7-H4B7-H3Lung cancerPD-L1Non-small cell lung cancerBackgroundSmall cell lung cancerAnti-tumor immune responseHuman small cell lung cancerQuantitative immunofluorescenceB7 family ligandsLevels of TILsMultiplexed quantitative immunofluorescenceLevels of CD3Effector T cellsImmune checkpoint blockersPromising clinical activityTissue microarray formatLymphocyte subsetsCheckpoint blockersOverall survivalLung malignancyClinicopathological variablesMarker levels