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 responseBlockers
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
2013
SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer
Dhodapkar KM, Gettinger SN, Das R, Zebroski H, Dhodapkar MV. SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer. OncoImmunology 2013, 2: e25205. PMID: 24073380, PMCID: PMC3782159, DOI: 10.4161/onci.25205.Peer-Reviewed Original ResearchNon-small cell lung carcinomaT cell responsesTumor-associated antigensClinical responseNSCLC patientsDisease regressionT cellsAntigen-specific T cell responsesAnti-PD-1 monoclonal antibodyNon-small cell lung cancerPD-1-blocking antibodiesPeripheral blood mononuclear cellsDeath-1 receptorImmune checkpoint blockadeCell lung cancerBlood mononuclear cellsLung cancer patientsCell lung carcinomaImportant tumor-associated antigenMajor oncogenic driverIntramolecular epitopeCheckpoint blockadeImmunotherapeutic strategiesTumor immunityHumoral responseHigh SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas
Velcheti V, Schalper K, Yao X, Cheng H, Kocoglu M, Dhodapkar K, Deng Y, Gettinger S, Rimm DL. High SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas. PLOS ONE 2013, 8: e61427. PMID: 23620753, PMCID: PMC3631238, DOI: 10.1371/journal.pone.0061427.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaLonger survivalTissue microarrayMultivariate analysisIndependent lung cancer cohortsIndependent positive prognostic markerSOX2 levelsNon-small cell lung carcinomaQuantitative immunofluorescenceLung squamous cell carcinomaSecond independent validation cohortSOX2 expressionHigh SOX2 levelsLog rank pSOX2 overexpressionPositive prognostic markerRisk of deathClinico-pathological characteristicsClinico-pathological variablesCox univariate analysisIndependent validation cohortCell lung carcinomaLung cancer cohortNSCLC patientsOverall survival