2022
Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer
Moutafi MK, Molero M, Morilla S, Baena J, Vathiotis IA, Gavrielatou N, Castro-Labrador L, de Garibay GR, Adradas V, Orive D, Valencia K, Calvo A, Montuenga LM, Aix S, Schalper KA, Herbst RS, Paz-Ares L, Rimm DL, Zugazagoitia J. Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004757. PMID: 36002182, PMCID: PMC9413286, DOI: 10.1136/jitc-2022-004757.Peer-Reviewed Original ResearchConceptsProgression-free survivalPD-1 axis blockadePD-1 axis inhibitorsTumor proportion scoreCell lung cancerAxis blockadeQuantitative immunofluorescenceAxis inhibitionLung cancerCD44 levelsCD44 expressionTumor compartmentsLonger progression-free survivalAbsence of immunotherapyYale Cancer CenterWhole tissue sectionsQIF scoresExternal independent validationMost patientsOverall survivalTim-3Immune compartmentImmunotherapy strategiesPD-L1Untreated cohort
2019
Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis
Datar I, Sanmamed MF, Wang J, Henick BS, Choi J, Badri T, Dong W, Mani N, Toki M, Mejías L, Lozano MD, Perez-Gracia JL, Velcheti V, Hellmann MD, Gainor JF, McEachern K, Jenkins D, Syrigos K, Politi K, Gettinger S, Rimm DL, Herbst RS, Melero I, Chen L, Schalper KA. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis. Clinical Cancer Research 2019, 25: 4663-4673. PMID: 31053602, PMCID: PMC7444693, DOI: 10.1158/1078-0432.ccr-18-4142.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDBiomarkers, TumorCarcinoma, Non-Small-Cell LungGene Expression Regulation, NeoplasticHepatitis A Virus Cellular Receptor 2HumansLung NeoplasmsLymphocyte ActivationLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingPrognosisProgrammed Cell Death 1 ReceptorRetrospective StudiesSingle-Cell AnalysisSurvival RateConceptsNon-small cell lung cancerHuman non-small cell lung cancerTumor-infiltrating lymphocytesAdvanced non-small cell lung cancerTim-3PD-1Cell lung cancerLAG-3Lung cancerPD-1 axis blockadeShorter progression-free survivalBaseline samplesTim-3 protein expressionMajor clinicopathologic variablesMultiplexed quantitative immunofluorescencePD-1 expressionProgression-free survivalTim-3 expressionLAG-3 expressionT-cell phenotypeTumor mutational burdenImmune inhibitory receptorsImmune evasion pathwaysTIM-3 proteinMass cytometry analysisSystematic 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
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