2023
Quantitative, 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
Association 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
Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer
Vathiotis IA, MacNeil T, Zugazagoitia J, Syrigos KN, Aung TN, Gruver AM, Vaillancourt P, Hughes I, Hinton S, Driscoll K, Rimm DL. Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer. Cancers 2021, 13: 1024. PMID: 33804482, PMCID: PMC7957629, DOI: 10.3390/cancers13051024.Peer-Reviewed Original ResearchLung cancer patientsCD200R expressionClinicopathologic characteristicsPD-L1Cancer patientsLung cancerImmune cellsLarge-cell neuroendocrine carcinoma patientsMutation statusNon-small cell lung cancer patientsCell lung cancer patientsQuantitative immunofluorescenceMultiplexed quantitative immunofluorescenceNeuroendocrine carcinoma patientsExpression of CD200Lung cancer cohortTumor cell stainingLCNEC patientsOverall survivalCarcinoma patientsImmune checkpointsImmune therapyTumor positivitySquamous differentiationCancer cohort
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 outcomesExpression 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 analysisExpression 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
2018
CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers
Pelekanou V, Villarroel-Espindola F, Schalper KA, Pusztai L, Rimm DL. CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers. Breast Cancer Research 2018, 20: 154. PMID: 30558648, PMCID: PMC6298021, DOI: 10.1186/s13058-018-1076-x.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic AgentsBiomarkers, TumorBreastBreast NeoplasmsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMatrix Metalloproteinase 9Middle AgedPatient SelectionPrognosisReceptors, Cell SurfaceReceptors, EstrogenRetrospective StudiesSurvival AnalysisTissue Array AnalysisTumor MicroenvironmentConceptsTumor-associated macrophagesOverall survivalQuantitative immunofluorescenceMacrophage markersBreast cancerHigh expressionPan-macrophage marker CD68Triple-negative breast cancerCD163/CD68Multiplexed quantitative immunofluorescenceImproved overall survivalProtein expressionWorse overall survivalPoor overall survivalMMP-9 protein expressionSubclass of patientsMacrophage-targeted therapiesMatrix metalloproteinase-9Tissue microarray formatMMP-9 proteinBreast tumor microenvironmentModulator of responseParaffin-embedded tissuesBreast cancer biomarkersCohort BImmune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations
Toki MI, Mani N, Smithy JW, Liu Y, Altan M, Wasserman B, Tuktamyshov R, Schalper K, Syrigos KN, Rimm DL. Immune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations. Journal Of Thoracic Oncology 2018, 13: 1884-1896. PMID: 30267840, PMCID: PMC6251746, DOI: 10.1016/j.jtho.2018.09.012.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPD-L1TIL activationHigh PD-L1 levelsDeath ligand 1 (PD-L1) expressionActivation statusKRAS wild-type tumorsKRAS mutantEGFR mutantsHigh PD-L1Multiplexed quantitative immunofluorescenceUnique immune profilePD-L1 levelsLigand 1 expressionDeath-1/EGFR-mutant tumorsImmunotherapy response ratesKRAS mutant tumorsWild-type tumorsHigher CD4NSCLC patientsImmune profileClinical efficacyKRAS WTLymphocyte populationsA dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nature Communications 2018, 9: 3196. PMID: 30097571, PMCID: PMC6086912, DOI: 10.1038/s41467-018-05032-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BlockingCarcinogenesisCarcinoma, Non-Small-Cell LungCell ProliferationCytotoxicity, ImmunologicHistocompatibility Antigens Class IHumansLung NeoplasmsLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred NODMice, SCIDMutant ProteinsMutationPeptidesPhenotypeProgrammed Cell Death 1 ReceptorReproducibility of ResultsSurvival AnalysisTobaccoConceptsImmune checkpoint blockersCheckpoint blockersQuantitative immunofluorescenceNon-small cell lung carcinoma patientsCell lung carcinoma patientsNon-small cell lung carcinomaPatient-derived xenograft modelsIntratumoral T cellsMultiplexed quantitative immunofluorescencePD-1 blockadeLevels of CD3Lung carcinoma patientsCell lung carcinomaT cell proliferationPre-treatment samplesTIL phenotypeSurvival benefitCarcinoma patientsEffector capacityLung carcinomaT cellsWhole-exome DNA sequencingXenograft modelFavorable responseBlockers
2017
Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer
Schalper KA, Carvajal-Hausdorf D, McLaughlin J, Altan M, Velcheti V, Gaule P, Sanmamed MF, Chen L, Herbst RS, Rimm DL. Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer. Clinical Cancer Research 2017, 23: 370-378. PMID: 27440266, PMCID: PMC6350535, DOI: 10.1158/1078-0432.ccr-16-0150.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterleukin-10Lymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingRNA, MessengerV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerB7-H4PD-L1IDO-1Lung cancerLung carcinomaQuantitative immunofluorescenceIFNγ stimulationElevated PD-L1Major clinicopathologic variablesMultiplexed quantitative immunofluorescenceOptimal clinical trialsT-cell infiltratesCell lung cancerImmune evasion pathwaysHuman lung carcinomaLung adenocarcinoma A549Cancer Genome AtlasClinicopathologic variablesMarker levelsClinical trialsStage ITherapeutic resistanceTCGA datasetA549 cells
2016
Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer
Mani NL, Schalper KA, Hatzis C, Saglam O, Tavassoli F, Butler M, Chagpar AB, Pusztai L, Rimm DL. Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer. Breast Cancer Research 2016, 18: 78. PMID: 27473061, PMCID: PMC4966732, DOI: 10.1186/s13058-016-0737-x.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientQuantitative immunofluorescenceBreast cancerSame cancerSingle biopsyMultiplexed quantitative immunofluorescenceTumor-infiltrating lymphocytesPotential predictive markerPrimary breast carcinomaCytokeratin-positive epithelial cellsCD20-positive lymphocytesCD8 levelsLymphocyte scoreQIF scoresLymphocyte countLymphocyte subpopulationsMultiple biopsiesSubpopulation countsPredictive markerPrognostic informationBreast carcinomaBiopsyB lymphocytesCD3Breast tumors