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 OS
2020
Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer
Bar N, Costa F, Das R, Duffy A, Samur M, McCachren S, Gettinger S, Neparidze N, Parker TL, Bailur JK, Pendleton K, Bajpai R, Zhang L, Xu ML, Anderson T, Giuliani N, Nooka A, Cho HJ, Raval A, Shanmugam M, Dhodapkar KM, Dhodapkar M. Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer. JCI Insight 2020, 5 PMID: 32427579, PMCID: PMC7406262, DOI: 10.1172/jci.insight.129353.Peer-Reviewed Original ResearchConceptsPD-L1 blockadePD-1 blockadeAsymptomatic multiple myelomaMonocyte-derived DCsPD-L1Immunologic effectsT cellsMyeloid cellsAntigen-specific T cell expansionAnti-PD-1 therapyMyeloid antigen-presenting cellsDistinct inflammatory signatureSystemic immunologic effectsLung cancer patientsT cell expansionAntigen-presenting cellsMyeloid activationMyeloid inflammationInflammatory signatureNIH/NCICheckpoint blockadeDC maturationL1 therapyCombination therapyInflammatory phenotypeImmune 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 therapy
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
2015
Immune Checkpoint Modulation for Non–Small Cell Lung Cancer
Soria JC, Marabelle A, Brahmer JR, Gettinger S. Immune Checkpoint Modulation for Non–Small Cell Lung Cancer. Clinical Cancer Research 2015, 21: 2256-2262. PMID: 25979932, DOI: 10.1158/1078-0432.ccr-14-2959.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerImmune checkpointsL1 antibodyLung cancerClinical trialsT cellsImmune-related progression-free survivalCytotoxic T-lymphocyte-associated protein 4Response rateT-lymphocyte-associated protein 4Tumor PD-L1 expressionRandomized phase II trialImmune checkpoint modulationObjective response ratePD-L1 expressionPhase II trialProgression-free survivalDeath ligand 1Immunosuppressive T cellsAdditional clinical trialsLung cancer patientsLow toxicity profileNSCLC histologyCombination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
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 responseBiomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study.
Powderly J, Koeppen H, Hodi F, Sosman J, Gettinger S, Desai R, Tabernero J, Soria J, Hamid O, Fine G, Xiao Y, Mokatrin A, Wu J, Anderson M, Irving B, Chen D, Kowanetz M. Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. Journal Of Clinical Oncology 2013, 31: 3001-3001. DOI: 10.1200/jco.2013.31.15_suppl.3001.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1Blood-based biomarkersPD-1T cellsPD-L1 tumor expressionTumor samplesT-cell gene signaturePD-L1 blockadeT cell infiltrationMetastatic solid tumorsPD-L1 upregulationT cell reactivationT cell subsetsImmune cell subsetsTumor immune microenvironmentPretreatment tumor samplesAvailable tumor tissueHuman monoclonal antibodyActivated T cellsT cell activationTumor CD8Expansion cohortAntitumor immunityBiopsy cohort