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
2018
Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer
Villarroel-Espindola F, Yu X, Datar I, Mani N, Sanmamed M, Velcheti V, Syrigos K, Toki M, Zhao H, Chen L, Herbst RS, Schalper KA. Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer. Clinical Cancer Research 2018, 24: 1562-1573. PMID: 29203588, PMCID: PMC5884702, DOI: 10.1158/1078-0432.ccr-17-2542.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntigens, CDAntigens, Differentiation, MyelomonocyticB7 AntigensB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesEvaluation Studies as TopicFemaleGene Expression Regulation, NeoplasticHumansImmunologic FactorsImmunotherapyLung NeoplasmsMaleMembrane ProteinsMutationProgrammed Cell Death 1 ReceptorRetrospective StudiesConceptsNon-small cell lung cancerHuman non-small cell lung cancerT helper cellsCytotoxic T cellsT cellsPD-1Localized expression patternQuantitative immunofluorescenceTumor-infiltrating lymphocytesCell lung cancerLung cancer casesGenomic analysisTissue microarray formatTumor-associated macrophagesPD-L1 proteinCytoplasmic staining patternClin Cancer ResExpression patternsLow mutational burdenTumor epithelial cellsSpecific genomic alterationsVISTA expressionVISTA proteinPD-L1Immunomodulatory role
2017
Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images
Wang X, Janowczyk A, Zhou Y, Thawani R, Fu P, Schalper K, Velcheti V, Madabhushi A. Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images. Scientific Reports 2017, 7: 13543. PMID: 29051570, PMCID: PMC5648794, DOI: 10.1038/s41598-017-13773-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedArea Under CurveCarcinoma, Non-Small-Cell LungCell NucleusCohort StudiesDiscriminant AnalysisFemaleHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisProportional Hazards ModelsRetrospective StudiesROC CurveTissue Array AnalysisConceptsNon-small cell lung cancerEarly-stage non-small cell lung cancerStage non-small cell lung cancerEarly-stage NSCLC patientsStage NSCLC patientsCell lung cancerPrediction of recurrenceDisease recurrenceNSCLC patientsLung cancerTissue microarrayMultivariable Cox proportional hazards modelsCox proportional hazards modelTraditional prognostic variablesIndependent prognostic factorIdentification of patientsProportional hazards modelAdjuvant therapyNodal statusPrognostic factorsRetrospective cohortValidation cohortTraining cohortPrognostic variablesHigh riskObjective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer
Carvajal-Hausdorf DE, Mani N, Velcheti V, Schalper KA, Rimm DL. Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2017, 5: 81. PMID: 29037255, PMCID: PMC5644103, DOI: 10.1186/s40425-017-0285-7.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsFemaleHumansLymphocytes, Tumor-InfiltratingMiddle AgedRetrospective StudiesSurvival AnalysisConceptsHormone receptor-positive breast cancerReceptor-positive breast cancerIDO1 expressionBreast cancerIndependent negative prognostic markerB cell infiltrationImmune suppressive pathwaysAdvanced solid tumorsTumor-infiltrating lymphocytesT cell responsesClinico-pathological featuresClinico-pathological characteristicsProportional hazards modelNegative prognostic markerDegradation of tryptophanMann-Whitney testFoxp3 levelsIDO1 blockadeIDO1 levelsEffector CD4Durable responsesOverall survivalImmune toleranceMultivariable analysisPrognostic markerObjective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2Carcinoma
2016
Automated measurement of estrogen receptor in breast cancer: a comparison of fluorescent and chromogenic methods of measurement
Zarrella ER, Coulter M, Welsh AW, Carvajal DE, Schalper KA, Harigopal M, Rimm D, Neumeister V. Automated measurement of estrogen receptor in breast cancer: a comparison of fluorescent and chromogenic methods of measurement. Laboratory Investigation 2016, 96: 1016-1025. PMID: 27348626, PMCID: PMC5008858, DOI: 10.1038/labinvest.2016.73.Peer-Reviewed Original ResearchQuantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer. JAMA Oncology 2016, 2: 1-9. PMID: 26562159, PMCID: PMC4941982, DOI: 10.1001/jamaoncol.2015.3638.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibody SpecificityB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLung NeoplasmsMaleObserver VariationPredictive Value of TestsReproducibility of ResultsRetrospective StudiesTissue Array AnalysisConceptsTumor-infiltrating lymphocytesPD-L1 expressionPD-L1 antibodiesPD-L1 protein expressionCell lung cancerPD-L1Whole tissue sectionsQuantitative immunofluorescenceLung cancerChromogenic immunohistochemistryPoor concordanceDifferent PD-L1 antibodiesHigh tumor-infiltrating lymphocytesTumor PD-L1 expressionPD-L1 protein levelsCell lung cancer biopsiesMonoclonal antibodiesCurrent consensus guidelinesProtein expressionDurable clinical responsesMain outcome measuresEarly phase trialsLung cancer biopsiesRabbit monoclonal antibodyCorresponding tissue microarrays
2015
Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer
Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, Herbst RS, Rimm DL. Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer. Journal Of The National Cancer Institute 2015, 107: dju435. PMID: 25650315, PMCID: PMC4565530, DOI: 10.1093/jnci/dju435.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD20Carcinoma, Non-Small-Cell LungCD3 ComplexCD8 AntigensConfounding Factors, EpidemiologicFluorescent DyesHumansIndolesKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMicroscopy, FluorescencePredictive Value of TestsRetrospective StudiesT-Lymphocytes, CytotoxicConceptsTumor-infiltrating lymphocytesLevels of CD3TIL subtypesMultivariable analysisTumor sizeLonger survivalAssociation of TILsLevel of TILsNon-small cell lung cancerNon-small cell lung cancer samplesLocal immune effectsClinico-pathologic characteristicsImmune checkpoint inhibitorsCell lung cancerCell lung cancer samplesLung cancer samplesDifferent tumor compartmentsObjective measurementsElevated CD3High CD20TIL markersTIL subpopulationsCheckpoint inhibitorsSmoking historyHistology type
2013
A Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/ College of American Pathologists Criteria
Schalper KA, Kumar S, Hui P, Rimm DL, Gershkovich P. A Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/ College of American Pathologists Criteria. Archives Of Pathology & Laboratory Medicine 2013, 138: 213-9. PMID: 24164555, DOI: 10.5858/arpa.2012-0617-oa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCarcinomaCohort StudiesConnecticutFemaleHospitals, UniversityHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMammary Glands, HumanMiddle AgedNeoplasm GradingNeoplasm InvasivenessNeoplasm ProteinsPractice Guidelines as TopicReceptor, ErbB-2Retrospective StudiesSocieties, MedicalUnited StatesUnited States Food and Drug Administration