2022
Inhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatment
2021
Quantitative immunofluorescence and mRNA analysis of immune-related biomarker groups in matched paired tumor samples from OPHELIA window study in head and neck squamous cell carcinoma (HNSCC).
Psyrri A, Moutafi M, Koliou G, Papaxoinis G, Gavrielatou N, Economopoulou P, Kotsantis I, Gkotzamanidou M, Anastasiou M, Pectasides D, Fernandez A, Yaghoobi V, Shafi S, Vathiotis I, Aung T, Gkolfinopoulos S, Foukas P, Fountzilas G, Rimm D. Quantitative immunofluorescence and mRNA analysis of immune-related biomarker groups in matched paired tumor samples from OPHELIA window study in head and neck squamous cell carcinoma (HNSCC). Journal Of Clinical Oncology 2021, 39: 6064-6064. DOI: 10.1200/jco.2021.39.15_suppl.6064.Peer-Reviewed Original ResearchCombined positive scorePD-L1 expressionQuantitative immunofluorescencePD-L1Preclinical modelsCD8 T cell infiltrationNeck squamous cell carcinomaPhase II trialReal-time quantitative reverse transcription polymerase chain reactionT cell infiltrationPD-L1 upregulationSquamous cell carcinomaPD-L1 mRNAQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionBiomarker groupsWindow studyTranscription-polymerase chain reactionSTING protein levelsPost-treatment samplesII trialAntitumor immunityImmune infiltratesPD-1Dual blockadeSpatially 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
2019
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomesMultiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry
Carvajal-Hausdorf DE, Patsenker J, Stanton KP, Villarroel-Espindola F, Esch A, Montgomery RR, Psyrri A, Kalogeras KT, Kotoula V, Foutzilas G, Schalper KA, Kluger Y, Rimm DL. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry. Clinical Cancer Research 2019, 25: 3054-3062. PMID: 30796036, PMCID: PMC6522272, DOI: 10.1158/1078-0432.ccr-18-2599.Peer-Reviewed Original ResearchConceptsTrastuzumab-treated patientsT cell infiltrationCD8 T cell infiltrationCohort of patientsCytotoxic T cellsMass cytometryCase-control seriesExtracellular domainMechanism of actionTrastuzumab benefitAdjuvant treatmentCD8 cellsRecurrence eventsT cellsAntibody panelImmune systemPatientsMetal-conjugated antibodiesQuantitative immunofluorescenceTrastuzumabImaging Mass CytometryHER2Signaling targetsObjective measurementsCytometry
2016
Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma
Vassilakopoulou M, Avgeris M, Velcheti V, Kotoula V, Rampias T, Chatzopoulos K, Perisanidis C, Kontos CK, Giotakis AI, Scorilas A, Rimm D, Sasaki C, Fountzilas G, Psyrri A. Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma. Clinical Cancer Research 2016, 22: 704-713. PMID: 26408403, DOI: 10.1158/1078-0432.ccr-15-1543.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellFemaleFollow-Up StudiesGene ExpressionHumansImmunohistochemistryKaplan-Meier EstimateLaryngeal NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPrognosisProportional Hazards ModelsRetrospective StudiesRisk FactorsRNA, MessengerConceptsLaryngeal squamous cell carcinomaSquamous cell carcinomaPrimary laryngeal squamous cell carcinomaPD-L1 expressionTumor-infiltrating lymphocytesPD-L1 mRNA expressionTIL densityCell carcinomaAssessment of TILsLaryngeal squamous cell cancerStromal tumor-infiltrating lymphocytesSuperior disease-free survivalTumor PD-L1 expressionMRNA expressionPD-L1 protein expressionPD-L1 mRNA levelsHigher TIL densityImmune checkpoint inhibitorsPD-L1 levelsDisease-free survivalT cell infiltrationSquamous cell cancerSecond independent cohortAdjacent tissue specimensFresh-frozen tumors
2015
Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites
Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, Rimm DL, Chen L, Jilaveanu LB. Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites. Clinical Cancer Research 2015, 21: 3052-3060. PMID: 25788491, PMCID: PMC4490112, DOI: 10.1158/1078-0432.ccr-14-3073.Peer-Reviewed Original ResearchConceptsPD-L1 expressionT-cell contentPD-1/PD-L1 inhibitorsHigher T-cell contentT-cell infiltratesPD-L1 inhibitorsAnatomic sitesBrain metastasesMetastatic melanomaTissue microarrayHigh PD-L1 expressionLess PD-L1 expressionLow PD-L1 expressionTumor PD-L1 expressionHigher TIL contentImproved overall survivalT cell infiltrationLess T cellsMetastatic melanoma samplesExtracerebral metastasesCerebral metastasesOverall survivalDermal metastasesImproved survivalPD-L1