2022
Multiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial.
Parra E, Duose D, Zhang J, Redman M, Segura R, Marques-Piubelli M, Fernandez C, Zhang B, Lindsay J, Moravec R, Kannan K, Luthra R, Alatrash G, Herbst R, Wistuba I, Gettinger S, Bazhenova L, Lee J, Zhang J, Haymaker C. Multiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial. Journal Of Clinical Oncology 2022, 40: 9046-9046. DOI: 10.1200/jco.2022.40.16_suppl.9046.Peer-Reviewed Original ResearchImmune checkpoint blockadeSquamous cell carcinomaT cellsBetter PFSLung cancerRecurrent squamous cell lung cancerTumor compartmentsLog-rank test analysisMetastatic lung squamous cell carcinomaSquamous cell lung cancerPD-1/CTLALung squamous cell carcinomaImmune cell scoreSingle-agent nivolumabDurable clinical benefitCD8 T cellsCell lung cancerCytotoxic immune cellsPositive clinical outcomesCell phenotypeFFPE tumor tissueBetter OSEligible patientsImmunogenomic profilingWorse OSRole of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer
de Rodas M, Nagineni V, Ravi A, Datar IJ, Mino-Kenudson M, Corredor G, Barrera C, Behlman L, Rimm DL, Herbst RS, Madabhushi A, Riess JW, Velcheti V, Hellmann MD, Gainor J, Schalper KA. Role of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004440. PMID: 35649657, PMCID: PMC9161072, DOI: 10.1136/jitc-2021-004440.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsT-cell immunoglobulin mucin-3Cell lung cancerCytotoxic T cellsT cellsImmune heterogeneityLung cancerT cell exhaustion marker expressionPD-L1 positive patientsT cell exhaustion markersAdaptive antitumor immune responsesCell death protein 1Baseline tumor samplesExhaustion marker expressionIndependent NSCLC cohortsTumor immune heterogeneityT-cell densityAntitumor immune responseT cell infiltrationDeath protein 1Multi-institutional cohortActivation gene-3Helper T cellsRole of tumor
2021
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer
2020
Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non–small-cell lung carcinoma
Boulle G, Velut Y, Mansuet-Lupo A, Gibault L, Blons H, Fournel L, Boni A, Cremer I, Wislez M, Duchatelle V, Trédaniel J, Hammond S, Herbst R, Alifano M, Giraud P, Damotte D. Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non–small-cell lung carcinoma. European Journal Of Cancer 2020, 135: 221-229. PMID: 32610210, DOI: 10.1016/j.ejca.2020.04.040.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesChemoradiotherapyChemoradiotherapy, AdjuvantFemaleForkhead Transcription FactorsHumansLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm StagingRetrospective StudiesTime FactorsTreatment OutcomeTumor MicroenvironmentConceptsT-cell densityCell lung carcinomaN2 NSCLCPatient survivalLung carcinomaClinical dataT cellsRadiotherapy efficacyIII-N2 NSCLCSurgery/chemotherapyPD-L1 expressionStandard of careImmunogenic cell deathDouble-positive cellsAction of radiotherapyIII-N2Immune environmentAbscopal effectChemoradiotherapy efficacyImmune infiltrationImmune cellsPositive cellsMultivariate analysisRadiotherapyTumor samplesImmune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapyComprehensive T cell repertoire characterization of non-small cell lung cancer
Reuben A, Zhang J, Chiou SH, Gittelman RM, Li J, Lee WC, Fujimoto J, Behrens C, Liu X, Wang F, Quek K, Wang C, Kheradmand F, Chen R, Chow CW, Lin H, Bernatchez C, Jalali A, Hu X, Wu CJ, Eterovic AK, Parra ER, Yusko E, Emerson R, Benzeno S, Vignali M, Wu X, Ye Y, Little LD, Gumbs C, Mao X, Song X, Tippen S, Thornton RL, Cascone T, Snyder A, Wargo JA, Herbst R, Swisher S, Kadara H, Moran C, Kalhor N, Zhang J, Scheet P, Vaporciyan AA, Sepesi B, Gibbons DL, Robins H, Hwu P, Heymach JV, Sharma P, Allison JP, Baladandayuthapani V, Lee JJ, Davis MM, Wistuba II, Futreal PA, Zhang J. Comprehensive T cell repertoire characterization of non-small cell lung cancer. Nature Communications 2020, 11: 603. PMID: 32001676, PMCID: PMC6992630, DOI: 10.1038/s41467-019-14273-0.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerT cellsLung cancerAdoptive T-cell therapyEarly-stage NSCLC patientsT cell repertoire analysisT cell responsesLungs of patientsT-cell therapyNSCLC patientsInferior survivalClinicopathologic featuresImmune landscapeViral infectionSolid tumorsTherapeutic efficacyCell responsesCell therapyPatientsRepertoire analysisLungTumorsImmunotherapyConsiderable proportion
2019
MA11.09 Increased Frequency of Bystander T Cells in the Lungs Is Associated with Recurrence in Localized Non-Small Cell Lung Cancer
Reuben A, Zhang J, Gittelman R, Chiou S, Li J, Fujimoto J, Behrens C, Kheradmand F, Chow C, Bernatchez C, Eterovic A, Benzeno S, Vignali M, Wu X, Ye Y, Cascone T, Herbst R, Swisher S, Kadara H, Moran C, Zhang J, Scheet P, Vaporciyan A, Sepesi B, Gibbons D, Robins H, Hwu P, Heymach J, Sharma P, Allison J, Lee J, Davis M, Wistuba I, Futreal P, Zhang J. MA11.09 Increased Frequency of Bystander T Cells in the Lungs Is Associated with Recurrence in Localized Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: s293. DOI: 10.1016/j.jtho.2019.08.589.Peer-Reviewed Original ResearchSystematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells
Dong MB, Wang G, Chow RD, Ye L, Zhu L, Dai X, Park JJ, Kim HR, Errami Y, Guzman CD, Zhou X, Chen KY, Renauer PA, Du Y, Shen J, Lam SZ, Zhou JJ, Lannin DR, Herbst RS, Chen S. Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells. Cell 2019, 178: 1189-1204.e23. PMID: 31442407, PMCID: PMC6719679, DOI: 10.1016/j.cell.2019.07.044.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCD8-Positive T-LymphocytesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCytokinesFemaleHumansImmunologic MemoryImmunotherapyMaleMiceMice, KnockoutNF-kappa BProgrammed Cell Death 1 ReceptorRNA HelicasesRNA, Guide, CRISPR-Cas SystemsTranscriptomeConceptsCRISPR screensTarget discoveryGenome-scale CRISPR screensCD8 TRNA helicase DHX37Vivo CRISPR screensGenetic screenGenome scaleTranscriptomic profilingBiochemical interrogationAntigen-specific CD8 TAnti-tumor immune responseFunctional regulatorTriple-negative breast cancerDHX37Essential roleTim-3PD-1Cytokine productionTumor infiltrationImmunotherapy targetImmunotherapy settingsRegulatorBreast cancerT cells
2018
A 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 responseBlockersSpatially 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
Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers.
Datar I, Mani N, Henick B, Wurtz A, Kaftan E, Herbst R, Rimm D, Gettinger S, Politi K, Schalper K. Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers. Journal Of Clinical Oncology 2017, 35: e14611-e14611. DOI: 10.1200/jco.2017.35.15_suppl.e14611.Peer-Reviewed Original ResearchNon-small cell lung carcinomaTim-3PD-1LAG-3T cellsInhibitory receptorsAdvanced non-small cell lung carcinomaPD-1 axis blockadeHigh TIM-3Immune suppressive pathwaysImmune inhibitory receptorsCell lung carcinomaMembranous staining patternPre-treatment samplesWhole tissue sectionsWhole tumor areaClinical responseMost patientsAxis blockadeLow levelsLung carcinomaT lymphocytesMultiplex immunofluorescenceHigh levelsSuppressive pathways