2023
Phase II window study of olaparib alone or with cisplatin or durvalumab in operable Head and Neck Cancer
Moutafi M, Koliou G, Papaxoinis G, Economopoulou P, Kotsantis I, Gkotzamanidou M, Anastasiou M, Pectasides D, Kyrodimos E, Delides A, Giotakis E, Papadimitriou N, Panayiotides I, Perisanidis C, Fernandez A, Xirou V, Poulios C, Gagari E, Yaghoobi V, Gavrielatou N, Shafi S, Aung T, Kougioumtzopoulou A, Kouloulias V, Palialexis K, Gkolfinopoulos S, Strati A, Lianidou E, Fountzilas G, Rimm D, Foukas P, Psyrri A. Phase II window study of olaparib alone or with cisplatin or durvalumab in operable Head and Neck Cancer. Cancer Research Communications 2023, 3: 1514-1523. PMID: 37575280, PMCID: PMC10414130, DOI: 10.1158/2767-9764.crc-23-0051.Peer-Reviewed Original ResearchConceptsObjective response rateTumor microenvironmentPD-L1Operable headResponse rateDeath ligand 1 (PD-L1) levelsPathologic complete response ratePhase II window studyNeck squamous cell carcinomaPD-L1 CPSComplete response rateSerious adverse eventsPercentage of patientsInhibitor-based treatmentSquamous cell carcinomaEffective antitumor responseImmunosuppressive tumor microenvironmentInflammatory tumor microenvironmentTumor cell proliferationColony-stimulating factor 1 receptor (CSF1R) genePrimary endpointSecondary endpointsAdverse eventsOpportunity trialAntitumor responseSubsets 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 patternsQuantitative, 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-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 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 ResearchConceptsImmune 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 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
Spatially Resolved and Quantitative Analysis of the Immunological Landscape in Human Meningiomas
Yeung J, Yaghoobi V, Aung TN, Vesely MD, Zhang T, Gaule P, Gunel M, Rimm DL, Chen L. Spatially Resolved and Quantitative Analysis of the Immunological Landscape in Human Meningiomas. Journal Of Neuropathology & Experimental Neurology 2021, 80: 150-159. PMID: 33393633, DOI: 10.1093/jnen/nlaa152.Peer-Reviewed Original ResearchConceptsPD-L1 expressionT cell infiltrationPD-L1PD-L2Human meningiomasTumor-infiltrating immune cell populationsHigh PD-L1 expressionT-cell activation/proliferationActivation/dysfunctionLevels of CD3Immune cell subsetsT-cell phenotypeImmune cell populationsHigh-grade tumorsActivation/proliferationHigher CD3TIL infiltrationCD8 ratioImmunotherapeutic strategiesCell subsetsImmunological statusGrade tumorsImmunological landscapeTissue microarrayMacrophage phenotype