2023
Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer
Ravi A, Hellmann M, Arniella M, Holton M, Freeman S, Naranbhai V, Stewart C, Leshchiner I, Kim J, Akiyama Y, Griffin A, Vokes N, Sakhi M, Kamesan V, Rizvi H, Ricciuti B, Forde P, Anagnostou V, Riess J, Gibbons D, Pennell N, Velcheti V, Digumarthy S, Mino-Kenudson M, Califano A, Heymach J, Herbst R, Brahmer J, Schalper K, Velculescu V, Henick B, Rizvi N, Jänne P, Awad M, Chow A, Greenbaum B, Luksza M, Shaw A, Wolchok J, Hacohen N, Getz G, Gainor J. Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer. Nature Genetics 2023, 55: 807-819. PMID: 37024582, PMCID: PMC10181943, DOI: 10.1038/s41588-023-01355-5.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungGenomicsHumansLung NeoplasmsProgrammed Cell Death 1 ReceptorTranscriptomeConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerLung cancerAnti-PD-1/PD-L1 agentsCheckpoint blockade responsePD-L1 agentsTumor intrinsic subtypesCheckpoint inhibitorsCheckpoint blockadeTreatment landscapeImmunotherapy outcomesBlockade responseCohortBiological determinantsGenomic subgroupsEnhanced responseMolecular featuresWhole exomeCancerProminent associationOutcomesAssociationResponseNumber of associations
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 roleMolecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand (PD-L)-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing
Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, Plodkowski A, Long N, Sauter JL, Rekhtman N, Hollmann T, Schalper KA, Gainor JF, Shen R, Ni A, Arbour KC, Merghoub T, Wolchok J, Snyder A, Chaft JE, Kris MG, Rudin CM, Socci ND, Berger MF, Taylor BS, Zehir A, Solit DB, Arcila ME, Ladanyi M, Riely GJ, Schultz N, Hellmann MD. Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand (PD-L)-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. Journal Of Clinical Oncology 2018, 36: jco.2017.75.338. PMID: 29337640, PMCID: PMC6075848, DOI: 10.1200/jco.2017.75.3384.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenCarcinoma, Non-Small-Cell LungExome SequencingHigh-Throughput Nucleotide SequencingHumansLung NeoplasmsMutationProgrammed Cell Death 1 ReceptorTumor BurdenConceptsImmune checkpoint inhibitorsDurable clinical benefitTumor mutation burdenPD-L1 expressionCell lung cancerTargeted Next-Generation SequencingWhole-exome sequencingLung cancerNext-generation sequencingPartial response/stable diseaseUse of ICIsAnti-programmed death-1Response/stable diseaseSolid Tumors version 1.1Anti-programmed cell deathProgression-free survivalResponse Evaluation CriteriaSubset of patientsPredictors of responseMultivariable predictive modelDetailed clinical annotationLack of benefitStable diseaseCheckpoint inhibitorsDurable responses
2016
Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer
Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL. Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Modern Pathology 2016, 30: 340-349. PMID: 27834350, PMCID: PMC5334264, DOI: 10.1038/modpathol.2016.186.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Non-Small-Cell LungFemaleHumansImmunohistochemistryLung NeoplasmsMaleProgrammed Cell Death 1 ReceptorReproducibility of ResultsConceptsPD-L1 expressionPD-L1Immune cellsImmune cell PD-L1 expressionNon-small cell lung cancerNon-small cell lung cancer (NSCLC) casesCell lung cancer casesTumor cellsPD-L1 assessmentStromal immune cellsPD-L1 positivityCell lung cancerLung cancer patientsLung cancer casesRepresentative tumor areasPathologist scoresLikelihood of responseConcordance correlation coefficientRabbit monoclonal antibodyIntraclass correlation coefficientCancer patientsLung cancerImmunohistochemistry slidesCancer casesTumor tissueAbscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming
Rodriguez-Ruiz ME, Rodriguez I, Garasa S, Barbes B, Solorzano JL, Perez-Gracia JL, Labiano S, Sanmamed MF, Azpilikueta A, Bolaños E, Sanchez-Paulete AR, Aznar MA, Rouzaut A, Schalper KA, Jure-Kunkel M, Melero I. Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming. Cancer Research 2016, 76: 5994-6005. PMID: 27550452, DOI: 10.1158/0008-5472.can-16-0549.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBasic-Leucine Zipper Transcription FactorsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalProgrammed Cell Death 1 ReceptorReceptor, Interferon alpha-betaRepressor ProteinsTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAnti-CD137 mAbsCD8 T cellsEffector T cellsT cellsTumor lesionsMyeloid-derived suppressor cellsSelective depletion experimentsType I IFN systemTumor-infiltrating lymphocytesCombination of radiotherapyField of irradiationImmunostimulatory mAbsImmunotherapy combinationsIntracellular IFNγProimmune effectsContralateral tumorsSuppressor cellsDendritic cellsClinical evidenceRadiotherapy strategiesIrradiation regimenAntitumor effectsClinical developmentTumor siteEx vivoPredictive 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 Research
2015
Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice
Sanmamed MF, Rodriguez I, Schalper KA, Oñate C, Azpilikueta A, Rodriguez-Ruiz ME, Morales-Kastresana A, Labiano S, Pérez-Gracia JL, Martín-Algarra S, Alfaro C, Mazzolini G, Sarno F, Hidalgo M, Korman AJ, Jure-Kunkel M, Melero I. Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice. Cancer Research 2015, 75: 3466-3478. PMID: 26113085, DOI: 10.1158/0008-5472.can-14-3510.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalColorectal NeoplasmsDNA-Binding ProteinsGraft vs Host DiseaseHT29 CellsHumansInterleukin Receptor Common gamma SubunitLeukocytes, MononuclearLymphocyte ActivationMiceNivolumabProgrammed Cell Death 1 ReceptorT-LymphocytesTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsPeripheral blood mononuclear cellsT lymphocytesHuman T lymphocytesAllogeneic human peripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsT cell-mediated diseaseImmune checkpoint drugsImmunostimulatory monoclonal antibodiesCell-mediated diseaseRegulatory T lymphocytesHumanized murine modelBlood mononuclear cellsHumanized mouse modelPreclinical model systemsLymphocyte infiltrationTherapeutic regimenMononuclear cellsCell surface expressionCancer immunologyGastric carcinomaImmunodeficient miceMurine modelMouse modelSame patientTumor xenografts