2024
Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee
Monette A, Warren S, Barrett J, Garnett-Benson C, Schalper K, Taube J, Topp B, Snyder A. Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee. Journal For ImmunoTherapy Of Cancer 2024, 12: e009427. PMID: 39032943, PMCID: PMC11261685, DOI: 10.1136/jitc-2024-009427.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorConsensusHumansImmune Checkpoint InhibitorsImmunotherapyNeoplasmsConceptsProgrammed cell death protein 1/programmed death-ligand 1PD-(L)1Biomarker developmentApplication of novel biomarkersPD-(L)1 therapyDeath-ligand 1Patient selection strategiesCombination therapyTumor typesTreatment optionsImmune biologyAxis inhibitionEffective treatmentCancer progressionNovel biomarkersPatientsTherapyImmunotherapyBiomarkersKnowledge of mechanismsDelivery of effective treatmentTreatmentAgentsTumorProgressionHigh-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
B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes
Altan M, Pelekanou V, Schalper KA, Toki M, Gaule P, Syrigos K, Herbst RS, Rimm DL. B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes. Clinical Cancer Research 2017, 23: 5202-5209. PMID: 28539467, PMCID: PMC5581684, DOI: 10.1158/1078-0432.ccr-16-3107.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB7 AntigensB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryLymphocytes, Tumor-InfiltratingMaleMiddle AgedPrognosisV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesB7-H3 proteinB7-H4PD-L1B7-H3Majority of NSCLCQuantitative immunofluorescenceImmune checkpoints PD-1Major clinicopathologic variablesLevels of CD3Negative prognostic impactCell lung cancerPoor overall survivalSuccessful therapeutic targetsB7 family membersClin Cancer ResB7-H1NSCLC cohortOverall survivalPrognostic impactSmoking historyClinicopathologic characteristicsPD-1Clinical stageInterleukin-8 in cancer pathogenesis, treatment and follow-up
Alfaro C, Sanmamed MF, Rodríguez-Ruiz ME, Teijeira Á, Oñate C, González Á, Ponz M, Schalper KA, Pérez-Gracia JL, Melero I. Interleukin-8 in cancer pathogenesis, treatment and follow-up. Cancer Treatment Reviews 2017, 60: 24-31. PMID: 28866366, DOI: 10.1016/j.ctrv.2017.08.004.Peer-Reviewed Original ResearchConceptsSerum concentrationsInterleukin-8IL-8 serum concentrationsPro-tumoral functionsCancer stem cellsTumor burdenLeukocyte infiltrateCancer immunotherapyIL-8Pharmacodynamic biomarkersTherapeutic combinationsTherapeutic strategiesMyeloid cellsTumor progressionCancer pathogenesisTumor cellsGrowth factorImmunotherapySuch interventionsChemokinesStem cellsCellsInfiltratesCXCR1/2PathogenesisDifferential 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
Strategies to design clinical studies to identify predictive biomarkers in cancer research
Perez-Gracia JL, Sanmamed MF, Bosch A, Patiño-Garcia A, Schalper KA, Segura V, Bellmunt J, Tabernero J, Sweeney CJ, Choueiri TK, Martín M, Fusco JP, Rodriguez-Ruiz ME, Calvo A, Prior C, Paz-Ares L, Pio R, Gonzalez-Billalabeitia E, Hernandez A, Páez D, Piulats JM, Gurpide A, Andueza M, de Velasco G, Pazo R, Grande E, Nicolas P, Abad-Santos F, Garcia-Donas J, Castellano D, Pajares MJ, Suarez C, Colomer R, Montuenga LM, Melero I. Strategies to design clinical studies to identify predictive biomarkers in cancer research. Cancer Treatment Reviews 2016, 53: 79-97. PMID: 28088073, DOI: 10.1016/j.ctrv.2016.12.005.Peer-Reviewed Original ResearchConceptsPredictive biomarkersSpecific patient populationsPromising candidate biomarkerCancer researchUnnecessary toxicityPatient populationMultidisciplinary panelClinical studiesReliable biomarkersAnti-cancer drugsCandidate biomarkersClinical designStudy designBiomarkersPromising targetBiomarker identification studiesKey biomarkersDrugsAnticancer drugsEfficient study designStandard practiceToxicityPatientsOncologyPivotal fieldEGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma
Toki MI, Carvajal-Hausdorf DE, Altan M, McLaughlin J, Henick B, Schalper KA, Syrigos KN, Rimm DL. EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma. Journal Of Thoracic Oncology 2016, 11: 1901-1911. PMID: 27449805, PMCID: PMC5075503, DOI: 10.1016/j.jtho.2016.06.025.Peer-Reviewed Original ResearchConceptsEGFR pathway activationSeries of patientsLung adenocarcinomaMutation statusEGFR expressionPathway activationProximity ligation assayKRAS wild-type tumorsEGFR-mutant patientsKRAS-mutant casesCohort of patientsWild-type tumorsInteraction of EGFREGFR expression levelsEGFR protein expressionMAPK/ERK pathwayGrowth factor receptorActive EGFRPrognostic factorsDifferent mutation statusPatient groupPrognostic valueLonger survivalEGFR mutationsPrognostic markerPredictive Biomarkers for PD-1 Axis Therapies: The Hidden Treasure or a Call for Research
Schalper KA, Kaftan E, Herbst RS. Predictive Biomarkers for PD-1 Axis Therapies: The Hidden Treasure or a Call for Research. Clinical Cancer Research 2016, 22: 2102-2104. PMID: 26957559, PMCID: PMC4940186, DOI: 10.1158/1078-0432.ccr-16-0169.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
Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer
Carvajal-Hausdorf DE, Schalper KA, Pusztai L, Psyrri A, Kalogeras KT, Kotoula V, Fountzilas G, Rimm DL. Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal Of The National Cancer Institute 2015, 107: djv136. PMID: 25991002, PMCID: PMC4554192, DOI: 10.1093/jnci/djv136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClinical Trials as TopicDisease-Free SurvivalExtracellular SpaceFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIntracellular SpaceKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisReceptor, ErbB-2Sensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment OutcomeConceptsHuman epidermal growth factor receptor 2ECD expressionICD statusLonger DFSQuantitative immunofluorescenceTrastuzumab therapyPrognostic valueBreast cancerTissue microarrayEpidermal growth factor receptor 2Adjuvant trastuzumab therapyDisease-free survival analysisTrastuzumab-treated patientsGrowth factor receptor 2High positive predictive valueHER2-positive tumorsKaplan-Meier estimatesFactor receptor 2ERBB2 gene amplificationHER2 protein expressionPositive predictive valueExtracellular domainAdjuvant chemotherapyHER2-ICDBetter DFSPD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer
Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunology Research 2015, 3: 326-332. PMID: 25527356, PMCID: PMC4390454, DOI: 10.1158/2326-6066.cir-14-0133.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesPD-L1 expressionPathologic complete responseNeoadjuvant chemotherapyPD-L1Breast cancerDeath 1 ligand 1PD-L1 protein expressionYale-New Haven HospitalHigh PD-L1Antitumor immune activitySubset of patientsTriple-negative patientsBreast cancer patientsTriple-negative statusImmune checkpoint proteinsImmune regulatory moleculesNew Haven HospitalSignificant multivariate modelRabbit monoclonal antibodyTILs correlateComplete responseImmune therapyCancer patientsImmune activity
2014
Quantitative measurement of cancer tissue biomarkers in the lab and in the clinic
Carvajal-Hausdorf D, Schalper KA, Neumeister V, Rimm DL. Quantitative measurement of cancer tissue biomarkers in the lab and in the clinic. Laboratory Investigation 2014, 95: 385-396. PMID: 25502176, PMCID: PMC4383674, DOI: 10.1038/labinvest.2014.157.Peer-Reviewed Original Research
2013
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation 2013, 94: 107-116. PMID: 24217091, PMCID: PMC6125250, DOI: 10.1038/labinvest.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorChi-Square DistributionCohort StudiesConnecticutFemaleGreeceHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMalePrognosisReproducibility of ResultsRNA, MessengerSurvival AnalysisTissue Array AnalysisConceptsNon-small cell lung cancerPD-L1 expressionCell lung cancerPD-L1Tissue microarrayBetter outcomesNSCLC casesLung cancerDeath ligand 1 (PD-L1) expressionCell death ligand 1PD-L1 protein expressionEarly phase clinical trialsLigand 1 expressionTumor-infiltrating lymphocytesDeath ligand 1Significant better outcomePD-L1 mRNAPD-L1 proteinPhase clinical trialsNormal human placentaPrediction of responseQuantitative fluorescence approachesFrequency of expressionPD-1Prognostic valueMarginal and Joint Distributions of S100, HMB-45, and Melan-A Across a Large Series of Cutaneous Melanomas
Viray H, Bradley WR, Schalper KA, Rimm DL, Rothberg BE. Marginal and Joint Distributions of S100, HMB-45, and Melan-A Across a Large Series of Cutaneous Melanomas. Archives Of Pathology & Laboratory Medicine 2013, 137: 1063-73. PMID: 23899062, PMCID: PMC3963468, DOI: 10.5858/arpa.2012-0284-oa.Peer-Reviewed Original ResearchConceptsHMB-45Primary tumorCutaneous melanomaLarge seriesMelanoma-specific survivalMelanoma primary tumorsGroup of antigensLarge tissue microarrayClinicopathologic covariatesClinicopathologic criteriaPrognostic relevanceHistopathologic profileClinicopathologic correlatesAntigen expressionClinicopathologic parametersMelanoma markersTissue microarrayPositive expressionSurvival analysisMelanomaMelanS100Melanoma cellsBivariate associationsSignificant differencesSarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1)
Velcheti V, Rimm DL, Schalper KA. Sarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1). Journal Of Thoracic Oncology 2013, 8: 803-805. PMID: 23676558, PMCID: PMC3703468, DOI: 10.1097/jto.0b013e318292be18.Peer-Reviewed Original ResearchConceptsDeath ligand 1Sarcomatoid carcinomaCell lung carcinomaLung carcinomaPD-L1PD-1/PD-L1 axisPD-1/PD-L1 pathwayProgrammed Death Ligand 1PD-L1 protein expressionEffector immune responsesPD-L1 axisPD-L1 pathwayLung sarcomatoid carcinomaLung cancer cohortSarcomatoid lung carcinomasLigand 1Mouse monoclonal antibodyDeath-1Lymphocytic infiltrationRare subtypeSuch therapyCancer cohortT cellsCarcinomaTumor types
2012
p16ink4a Expression in Benign and Malignant Melanocytic Conjunctival Lesions
Zoroquiain P, Fernandes BF, González S, Novais GN, Schalper KA, Burnier MN. p16ink4a Expression in Benign and Malignant Melanocytic Conjunctival Lesions. International Journal Of Surgical Pathology 2012, 20: 240-245. PMID: 22287653, DOI: 10.1177/1066896911435697.Peer-Reviewed Original ResearchConceptsConjunctival melanocytic lesionsImmunoreactive scoreMelanocytic lesionsGerman immunoreactive scoreMean immunoreactive scoreRoutine microscopic analysisMalignant melanocytic lesionsConjunctival melanomaConjunctival lesionsImmunohistochemical expressionImmunohistochemical studyMortality rateHigh metastasisLarge seriesMalignant melanocytic neoplasmsLesionsP16 expressionMelanomaGood markerNeviAdditional studiesMelanocytic neoplasmsAtypiaUnfavorable locationP16