2024
Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay
Liu M, Vathiotis I, Robbins C, Chan N, Moutafi M, Burela S, Xirou V, Schalper K, Herbst R, Syrigos K, Rimm D. Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay. Modern Pathology 2024, 37: 100556. PMID: 38964502, PMCID: PMC11416319, DOI: 10.1016/j.modpat.2024.100556.Peer-Reviewed Original ResearchNon-small cell lung cancerCases of non-small cell lung cancerNon-small cell lung cancer casesT-DXdCell lung cancerHER2 expressionBreast cancerRare case of non-small cell lung cancerQuantitative immunofluorescenceAntibody-drug conjugate trastuzumab deruxtecanLung cancerHER2 antibody-drug conjugatesNon-small cell lung cancer patientsDetecting HER2 expressionHER2-targeted therapyMetastatic breast cancerHER2 protein expressionBreast cancer casesHER2 protein levelsAntibody-drug conjugatesProportion of casesTrastuzumab deruxtecanNSCLC casesFrequency of casesImmunohistochemistry scoreHigh-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
Deep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer
Barrera C, Corredor G, Viswanathan V, Ding R, Toro P, Fu P, Buzzy C, Lu C, Velu P, Zens P, Berezowska S, Belete M, Balli D, Chang H, Baxi V, Syrigos K, Rimm D, Velcheti V, Schalper K, Romero E, Madabhushi A. Deep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer. Npj Precision Oncology 2023, 7: 52. PMID: 37264091, PMCID: PMC10235089, DOI: 10.1038/s41698-023-00403-x.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor-infiltrating lymphocytesLung cancerEffective adaptive immune responseImmune checkpoint blockersCell lung cancerLung cancer patientsTumor immune microenvironmentAdaptive immune responsesImmune-related biomarkersTreatment-specific outcomesCheckMate 057Histology variantsImmunotherapy resistanceCheckpoint blockersRegulatory cellsTumor rejectionTumor-immune interactionsClinical outcomesImmunosuppressive signalsClinical benefitInfluence prognosisImmune microenvironmentCancer patientsPatient outcomesQuantitative, 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 ResearchConceptsNon-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-2
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 heterogeneityAssociation 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 cancerComparison 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
A prognostic model for overall survival of patients with early-stage non-small cell lung cancer: a multicentre, retrospective study
Lu C, Bera K, Wang X, Prasanna P, Xu J, Janowczyk A, Beig N, Yang M, Fu P, Lewis J, Choi H, Schmid RA, Berezowska S, Schalper K, Rimm D, Velcheti V, Madabhushi A. A prognostic model for overall survival of patients with early-stage non-small cell lung cancer: a multicentre, retrospective study. The Lancet Digital Health 2020, 2: e594-e606. PMID: 33163952, PMCID: PMC7646741, DOI: 10.1016/s2589-7500(20)30225-9.Peer-Reviewed Original ResearchConceptsNon-small cell lung carcinomaEarly-stage non-small cell lung carcinomaOverall survivalRetrospective studyEarly-stage non-small cell lung cancerNon-small cell lung cancerMultivariable Cox regression analysisCell differentiation pathwayCox proportional hazards modelLung squamous cell carcinomaEarly-stage LUADOverall survival informationCox regression analysisPrognosis of patientsCell lung cancerRisk stratification modelSquamous cell carcinomaLung cancer pathogenesisIndependent validation cohortCell lung carcinomaProportional hazards modelComputer-extracted featuresAdjuvant therapyDifferentiation pathwayValidation cohortBiomarkers 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 microarrayPD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC).
Doroshow D, Wei W, Zugazagoitia J, Robbins C, Gupta S, Adamson B, Rimm D. PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2020, 38: 9539-9539. DOI: 10.1200/jco.2020.38.15_suppl.9539.Peer-Reviewed Original ResearchPD-L1 tumor proportion scoreNon-small cell lung cancerTumor proportion scoreMedian overall survivalFirst-line pembrolizumabOverall survivalLonger OSHazard ratioPD-L1Predictive biomarkersNS patientsProportion scoreSquamous non-small cell lung cancerAppropriate predictive biomarkersUnadjusted hazard ratioNSCLC tumor cellsLonger overall survivalCell lung cancerCheckpoint inhibitor useDe-identified databaseHistology interactionNonsquamous cancerSQ patientsSquamous histologyPrimary endpoint
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 outcomesMA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer
Wang X, Barrera C, Bera K, Lu C, Feldman M, Schalper K, Rimm D, Velcheti V, Madabhushi A. MA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: s350-s351. DOI: 10.1016/j.jtho.2019.08.710.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor-Infiltrating LymphocytesCell lung cancerLung cancerLymphocytesCancerHigh-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkersImmunotherapy 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 levelsSpatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer
Corredor G, Wang X, Zhou Y, Lu C, Fu P, Syrigos K, Rimm DL, Yang M, Romero E, Schalper KA, Velcheti V, Madabhushi A. Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer. Clinical Cancer Research 2019, 25: 1526-1534. PMID: 30201760, PMCID: PMC6397708, DOI: 10.1158/1078-0432.ccr-18-2013.Peer-Reviewed Original Research