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 ResearchConceptsNon-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-2
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 heterogeneityObjective assessment of tumor infiltrating lymphocytes as a prognostic marker in melanoma using machine learning algorithms
Aung TN, Shafi S, Wilmott JS, Nourmohammadi S, Vathiotis I, Gavrielatou N, Fernandez A, Yaghoobi V, Sinnberg T, Amaral T, Ikenberg K, Khosrotehrani K, Osman I, Acs B, Bai Y, Martinez-Morilla S, Moutafi M, Thompson JF, Scolyer RA, Rimm DL. Objective assessment of tumor infiltrating lymphocytes as a prognostic marker in melanoma using machine learning algorithms. EBioMedicine 2022, 82: 104143. PMID: 35810563, PMCID: PMC9272337, DOI: 10.1016/j.ebiom.2022.104143.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesMelanoma patientsPrognostic valuePrognostic markerPrimary melanoma patientsRobust prognostic markerStage II patientsSpecific molecular subtypesTIL phenotypeAdjuvant therapyOverall survivalSurgical treatmentTIL scoreII patientsSurvival outcomesLung cancerClinical trialsPrimary melanomaClinical impactT cellsMolecular subtypesHigh riskIndependent cohortLower riskEosin stainingQuantitative 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 heterogeneityDevelopment 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 ResearchConceptsSiglec-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 ResearchConceptsNon-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
2021
240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling
Moutafi M, Martinez-Morilla S, Divakar P, Vathiotis I, Gavrielatou N, Aung T, Yaghoobi V, Fernandez A, Fraile J, Schalper K, Rimm D. 240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling. 2021, a258-a258. DOI: 10.1136/jitc-2021-sitc2021.240.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPre-treatment samplesQuantitative immunofluorescencePredictive biomarkersLung cancerHigh PD-L1 expressionExpression of CD66bInitial biomarker discoveryOperable NSCLC patientsStromal immune cellsTwo-sided significance levelPD-L1 expressionImmune checkpoint blockadeRole of neutrophilsCell lung cancerPotential predictive biomarkersGood predictive valueDigital spatial profilingDigital Spatial ProfilerCohort validationICI therapyCheckpoint inhibitorsCheckpoint blockadeNSCLC cohortNSCLC patientsQuantitative Assessment of CD200 and CD200R Expression in Lung Cancer
Vathiotis IA, MacNeil T, Zugazagoitia J, Syrigos KN, Aung TN, Gruver AM, Vaillancourt P, Hughes I, Hinton S, Driscoll K, Rimm DL. Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer. Cancers 2021, 13: 1024. PMID: 33804482, PMCID: PMC7957629, DOI: 10.3390/cancers13051024.Peer-Reviewed Original ResearchLung cancer patientsCD200R expressionClinicopathologic characteristicsPD-L1Cancer patientsLung cancerImmune cellsLarge-cell neuroendocrine carcinoma patientsMutation statusNon-small cell lung cancer patientsCell lung cancer patientsQuantitative immunofluorescenceMultiplexed quantitative immunofluorescenceNeuroendocrine carcinoma patientsExpression of CD200Lung cancer cohortTumor cell stainingLCNEC patientsOverall survivalCarcinoma patientsImmune checkpointsImmune therapyTumor positivitySquamous differentiationCancer cohort
2019
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
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