2023
Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Nature Medicine 2023, 29: 1718-1727. PMID: 37429923, DOI: 10.1038/s41591-023-02385-6.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerCell lung cancerSafety profileCombination therapyLung cancerInvestigator-assessed objective response rateRandomized phase 2 studySolid Tumors version 1.1T-cell-inflamed gene expression profileGroup IIIBiomarker-defined subgroupsFirst-line pembrolizumabPhase 2 studyProgression-free survivalResponse Evaluation CriteriaSubset of patientsHeterogenous tumor microenvironmentData cutoffOverall survivalSecondary outcomesPrimary outcomeTreatment armsTMB assessment
2022
Addressing CPI resistance in NSCLC: targeting TAM receptors to modulate the tumor microenvironment and future prospects
Peters S, Paz-Ares L, Herbst RS, Reck M. Addressing CPI resistance in NSCLC: targeting TAM receptors to modulate the tumor microenvironment and future prospects. Journal For ImmunoTherapy Of Cancer 2022, 10: e004863. PMID: 35858709, PMCID: PMC9305809, DOI: 10.1136/jitc-2022-004863.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungC-Mer Tyrosine KinaseHumansLung NeoplasmsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentConceptsImmunosuppressive tumor microenvironmentCheckpoint inhibitorsTAM receptorsImmune responseTumor microenvironmentOverall survivalLung cancerStandard first-line therapyLong-term clinical responseCell death protein 1Immunostimulatory tumor microenvironmentImmune checkpoint inhibitorsInhibitor-based regimensFirst-line therapyAntitumor immune responseDeath protein 1Cell lung cancerPatients' overall survivalStrong biological rationaleNew treatment approachesLong-term survivalActivation of Tyro3Majority of casesCPI therapyAdvanced NSCLC
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 samples
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 outcomes
2018
Defining and Understanding Adaptive Resistance in Cancer Immunotherapy
Kim TK, Herbst RS, Chen L. Defining and Understanding Adaptive Resistance in Cancer Immunotherapy. Trends In Immunology 2018, 39: 624-631. PMID: 29802087, PMCID: PMC6066429, DOI: 10.1016/j.it.2018.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAntibodies, MonoclonalB7-H1 AntigenDrug ResistanceImmunotherapyNeoplasmsProgrammed Cell Death 1 ReceptorTumor EscapeTumor MicroenvironmentConceptsAnti-PD therapyLong-term survival benefitAvailable treatment regimensFraction of respondersSurvival benefitTumor immunityTumor-immune interactionsAdvanced cancerTreatment regimensCancer immunotherapyTumor regressionTherapyAccurate tissueSuch treatmentAdaptive resistancePatientsMolecular mechanismsTrue resistanceImmunotherapyRegimensRight targetCancerRespondersImmunityAppropriate interpretationThe biology and management of non-small cell lung cancer
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018, 553: 446-454. PMID: 29364287, DOI: 10.1038/nature25183.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerSmall molecule tyrosine kinase inhibitorsMolecule tyrosine kinase inhibitorsBroader patient populationTyrosine kinase inhibitorsUnprecedented survival benefitsMetastatic diseaseMultimodal careSurvival benefitClinical benefitCombination therapyOverall curePatient populationSurvival rateTumor progressionEarly detectionKinase inhibitorsNew drugsDisease biologyCancerImmunotherapyPatientsTherapy
2017
Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases
Stevens LE, Cheung WKC, Adua SJ, Arnal-Estapé A, Zhao M, Liu Z, Brewer K, Herbst RS, Nguyen DX. Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases. Cancer Research 2017, 77: 1905-1917. PMID: 28196904, PMCID: PMC5468792, DOI: 10.1158/0008-5472.can-16-1978.Peer-Reviewed Original ResearchConceptsBrain metastatic nicheRisk of relapseDistant metastasisPoor prognosisLUAD subtypesLung tumorsLung adenocarcinomaLUAD cellsMetastatic outgrowthMetastatic nicheCancer ResCancer cellsECM-mediated signalingExtracellular matrix moleculesCell survivalMolecular signaturesDifferential expressionHMMRMatrix moleculesImportant mechanismCellsRelapseAdenocarcinomaPrognosisMetastasis