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
Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenHumansImmune Checkpoint InhibitorsIpilimumabMelanomaNivolumabTumor MicroenvironmentConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patternsDigital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchMeSH KeywordsCarcinomaHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survival
2022
Quantitative 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 analysisNSCLCPatients
2021
Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry
Martinez-Morilla S, Villarroel-Espindola F, Wong PF, Toki MI, Aung TN, Pelekanou V, Bourke-Martin B, Schalper KA, Kluger HM, Rimm DL. Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry. Clinical Cancer Research 2021, 27: 1987-1996. PMID: 33504554, PMCID: PMC8026677, DOI: 10.1158/1078-0432.ccr-20-3340.Peer-Reviewed Original ResearchMeSH KeywordsBeta 2-MicroglobulinBiomarkers, TumorHumansImage CytometryImmune Checkpoint InhibitorsMelanomaRNA, MessengerTissue Array AnalysisTumor Microenvironment