2024
High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC)
Moutafi M, Bates K, Aung T, Milian R, Xirou V, Vathiotis I, Gavrielatou N, Angelakis A, Schalper K, Salichos L, Rimm D. High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2024, 12: e009039. PMID: 38857914, PMCID: PMC11168162, DOI: 10.1136/jitc-2024-009039.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsProgrammed cell death protein 1Associated with OSCell lung cancerTissue microarray spotsTissue microarrayValidation cohortLung cancerNon-small cell lung cancer treated with immune checkpoint inhibitorsAssociated with resistance to immunotherapyCell death protein 1Resistance to immunotherapyAssociated with PFSProgression-free survivalSecreted frizzled-related protein 2Cox proportional-hazards model analysisCheckpoint inhibitorsImmunotherapy strategiesTumor compartmentsRetrospective cohortDiscovery cohortLong-term benefitsPatientsCD68
2023
Quantitative, Spatially Defined Expression of Leukocyte Associated Immunoglobulin-like Receptor (LAIR-1) in Non-Small Cell Lung Cancer
Aung T, Gavrielatou N, Vathiotis I, Fernandez A, Shafi S, Yaghoobi V, Burela S, MacNeil T, Ahmed F, Myint H, Flies D, Langermann S, Rimm D. Quantitative, Spatially Defined Expression of Leukocyte Associated Immunoglobulin-like Receptor (LAIR-1) in Non-Small Cell Lung Cancer. Cancer Research Communications 2023, 3: 471-482. PMID: 36960400, PMCID: PMC10029762, DOI: 10.1158/2767-9764.crc-22-0334.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunoglobulinsLeukocytesLung NeoplasmsConceptsNon-small cell lung cancerLeukocyte-associated immunoglobulin-like receptor-1LAIR-1 expressionMultiplexed quantitative immunofluorescenceCell lung cancerLung adenocarcinomaLung cancerPD-L1Anti-PD-1/PD-L1Anti-PD-1 resistanceSquamous cell carcinoma subtypeImmunoglobulin-like receptor-1Cancer immunotherapeutic strategiesDeath-1 blockadeResistant lung tumorsImmunoglobulin-like receptorsCell typesAntitumor immunityImmunotherapeutic strategiesHistologic subtypePrognostic valueCombination therapyLung tumorsCarcinoma subtypesLAIR-2Spatial characterization and quantification of CD40 expression across cancer types
Bates K, Vathiotis I, MacNeil T, Ahmed F, Aung T, Katlinskaya Y, Bhattacharya S, Psyrri A, Yea S, Parkes A, Sadraei N, Roychoudhury S, Rimm D, Gavrielatou N. Spatial characterization and quantification of CD40 expression across cancer types. BMC Cancer 2023, 23: 220. PMID: 36894898, PMCID: PMC9996913, DOI: 10.1186/s12885-023-10650-7.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Non-Small-Cell LungCD40 AntigensFemaleHumansLung NeoplasmsOvarian NeoplasmsPancreatic NeoplasmsConceptsCD40 expressionSolid tumorsTumor cellsQuantitative immunofluorescencePatient cohortPancreatic cancerCancer typesExpression of CD40Large patient cohortOvarian cancer populationTissue microarray formatDifferent solid tumorsInnate immune responseTNF receptor family membersAvailable patient cohortNSCLC populationOverall survivalPrognostic impactReceptor family membersCancer populationAdenocarcinoma populationImmune cellsOvarian cancerPancreatic adenocarcinomaPositivity rate
2022
Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityProgrammed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC
Fernandez AI, Gavrielatou N, McCann L, Shafi S, Moutafi MK, Martinez-Morilla S, Vathiotis IA, Aung TN, Yaghoobi V, Bai Y, Chan YG, Weidler J, Herbst R, Bates M, Rimm DL. Programmed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC. Journal Of Thoracic Oncology 2022, 17: 1078-1085. PMID: 35764237, DOI: 10.1016/j.jtho.2022.06.007.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunotherapyLigandsLung NeoplasmsPredictive Value of TestsReal-Time Polymerase Chain ReactionRetrospective StudiesRNA, MessengerConceptsImmune checkpoint inhibitorsHigh negative predictive valueLow stage patientsICI therapyPD-L1Negative predictive valueAdjuvant settingLong-term benefitsPredictive valueProgrammed Death Ligand 1PD-L1 mRNA levelsCurrent predictive biomarkersHigh PD-L1Death ligand 1Lung cancer managementPD-L1 mRNAUseful objective methodReal-time reverse transcription-polymerase chain reactionMRNA levelsStandard of careReverse transcription-polymerase chain reactionQuantitative real-time reverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMRNA expression levelsAdvanced NSCLCQuantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer
Shafi S, Aung TN, Xirou V, Gavrielatou N, Vathiotis IA, Fernandez A, Moutafi M, Yaghoobi V, Herbst RS, Liu LN, Langermann S, Rimm DL. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 35581307, PMCID: PMC10211373, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityDiscovery of Biomarkers of Resistance to Immune Checkpoint Blockade in NSCLC Using High-Plex Digital Spatial Profiling
Moutafi M, Martinez-Morilla S, Divakar P, Vathiotis I, Gavrielatou N, Aung TN, Yaghoobi V, Fernandez AI, Zugazagoitia J, Herbst R, Schalper KA, Rimm DL. Discovery of Biomarkers of Resistance to Immune Checkpoint Blockade in NSCLC Using High-Plex Digital Spatial Profiling. Journal Of Thoracic Oncology 2022, 17: 991-1001. PMID: 35490853, PMCID: PMC9356986, DOI: 10.1016/j.jtho.2022.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorCarcinoma, Non-Small-Cell LungHumansImmune Checkpoint InhibitorsLung NeoplasmsConceptsImmune checkpoint inhibitorsICI resistanceDigital spatial profilingICI therapyOverall survivalPretreatment samplesQuantitative immunofluorescenceImmune checkpoint blockadeRole of neutrophilsShorter overall survivalCandidate biomarker proteinsCandidate protein biomarkersCohort validationOperable NSCLCUntreated NSCLCCheckpoint inhibitorsCheckpoint blockadeCD66b expressionAdditional patientsClinical efficacyPoor outcomeDiscovery of biomarkersUnivariate analysisNSCLCPatientsDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunohistochemistryLung NeoplasmsSialic Acid Binding Immunoglobulin-like LectinsConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordanceAssociation of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer
Gavrielatou N, Liu Y, Vathiotis I, Zugazagoitia J, Aung TN, Shafi S, Fernandez A, Schalper K, Psyrri A, Rimm DL. Association of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer. Clinical Cancer Research 2022, 28: clincanres.2649.2021. PMID: 34686497, PMCID: PMC8776595, DOI: 10.1158/1078-0432.ccr-21-2649.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunotherapyLung NeoplasmsProgrammed Cell Death 1 ReceptorRetrospective StudiesConceptsNon-small cell lung cancerBest overall responsePD-L1 tumor proportion scorePD-1/PD-L1Immune checkpoint inhibitorsProgression-free survivalTumor proportion scoreCell lung cancerPD-L1Immunotherapy outcomesCheckpoint inhibitorsOverall survivalQuantitative immunofluorescenceLung cancerProportion scoreAdvanced non-small cell lung cancerLocal T cell responsesCell death protein 1Immunotherapy-treated patientsMultiplexed quantitative immunofluorescencePD-1 expressionPD-L1 expressionDeath protein 1Selection of patientsT cell responses
2019
Yiqi Chutan Tang Reduces Gefitinib‐Induced Drug Resistance in Non‐Small‐Cell Lung Cancer by Targeting Apoptosis and Autophagy
Zhang J, Sun L, Cui J, Wang J, Liu X, Aung T, Qu Z, Chen Z, Adelson D, Lin L. Yiqi Chutan Tang Reduces Gefitinib‐Induced Drug Resistance in Non‐Small‐Cell Lung Cancer by Targeting Apoptosis and Autophagy. Cytometry Part A 2019, 97: 70-77. PMID: 31411813, PMCID: PMC7004076, DOI: 10.1002/cyto.a.23869.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsApoptosisAutophagyCarcinoma, Non-Small-Cell LungCell ProliferationDrug Resistance, NeoplasmGefitinibHumansLung NeoplasmsMutationProtein Kinase InhibitorsQuinazolinesConceptsEpidermal growth factor receptor tyrosine kinase inhibitorsEGFR mutationsGrowth factor receptor tyrosine kinase inhibitorsDrug resistanceReceptor tyrosine kinase inhibitorsEGFR TKI-resistant cellsEGFR-TKI resistanceNew treatment strategiesGefitinib-induced apoptosisAnti-cancer effectsLower survival rateWestern blot analysisMonths treatmentMost patientsNSCLC patientsCell cycle arrestTreatment strategiesHigh incidenceMortality rateSurvival rateCancer leadFlow cytometryPatientsResistant cellsKinase inhibitorsAn effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer
Zhang J, Qu Z, Yao H, Sun L, Harata-Lee Y, Cui J, Aung TN, Liu X, You R, Wang W, Hai L, Adelson DL, Lin L. An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer. Biomedicine & Pharmacotherapy 2019, 118: 109169. PMID: 31310954, DOI: 10.1016/j.biopha.2019.109169.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsAutophagyCarcinoma, Non-Small-Cell LungCell Line, TumorCell SurvivalDown-RegulationDrug Resistance, NeoplasmDrugs, Chinese HerbalGefitinibGene Expression Regulation, NeoplasticHumansLung NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesUp-RegulationConceptsNon-small cell lung cancerCompound Kushen InjectionPI3K/AKT/mTOR pathwayCell lung cancerAKT/mTOR pathwayLung cancerGefitinib treatmentMTOR pathwayFirst-line treatment optionDrug sensitivityPositive EGFR mutationDose-dependent fashionSensitive cell linesMost patientsTreatment optionsEGFR mutationsKushen InjectionTreatment relapseSensitizing agentGefitinibCancerRegulation of autophagyDown regulationTreatment effectsPatients