2024
An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers
Xirou V, Moutafi M, Bai Y, Nwe Aung T, Burela S, Liu M, Kimple R, Shabbir Ahmed F, Schultz B, Flieder D, Connolly D, Psyrri A, Burtness B, Rimm D. An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers. Oral Oncology 2024, 152: 106750. PMID: 38547779, PMCID: PMC11060915, DOI: 10.1016/j.oraloncology.2024.106750.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesHead and neck cancerTILs evaluationHPV-positiveNeck cancerPrognostic valueHead and neck squamous cell cancer casesTIL variablesAssociated with favorable prognosisHPV-negative headHPV-negative populationHematoxylin-eosin-stained sectionsCox regression analysisPotential clinical implicationsInter-observer variabilityInfiltrating lymphocytesClinicopathological factorsFavorable prognosisValidation cohortTumor cellsCancer casesProspective settingQuPath softwareRetrospective collectionPredictive significance
2023
Spatial 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 ResearchConceptsCD40 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
2021
Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study
Taube JM, Roman K, Engle EL, Wang C, Ballesteros-Merino C, Jensen SM, McGuire J, Jiang M, Coltharp C, Remeniuk B, Wistuba I, Locke D, Parra ER, Fox BA, Rimm DL, Hoyt C. Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. Journal For ImmunoTherapy Of Cancer 2021, 9: e002197. PMID: 34266881, PMCID: PMC8286792, DOI: 10.1136/jitc-2020-002197.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 axisPD-L1 axisMultiplexed immunofluorescenceTumor cellsBreast carcinomaNon-small cell lung cancer (NSCLC) tissuesCell lung cancer tissuesCell density assessmentPD-L1 expressionLung cancer tissuesTissue sectionsPercent positive cellsAverage concordanceClinical laboratory processPDL1 expressionMIF assayPD-1PD-L1Predictive biomarkersLow-level expressionPositive cellsCancer tissuesFluorescent detection reagentMultisite trialChromogenic assayPutting the Microenvironment into the Immunotherapy Companion Diagnostic
Moutafi M, Rimm DL. Putting the Microenvironment into the Immunotherapy Companion Diagnostic. Clinical Cancer Research 2021, 27: 3812-3814. PMID: 33986024, DOI: 10.1158/1078-0432.ccr-21-1238.Peer-Reviewed Original Research
2020
Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Rozenblit M, Huang R, Danziger N, Hegde P, Alexander B, Ramkissoon S, Blenman K, Ross JS, Rimm DL, Pusztai L. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. Journal For ImmunoTherapy Of Cancer 2020, 8: e001558. PMID: 33239417, PMCID: PMC7689582, DOI: 10.1136/jitc-2020-001558.Peer-Reviewed Original ResearchConceptsPD-L1 positivity ratePD-L1 positivityPD-L1 expressionDifferent metastatic sitesPrimary tumorMetastatic sitesPositivity rateImmune cellsMetastatic lesionsTumor cellsPD-L1 protein expressionTriple-negative breast cancerMore primary tumorsTriple negative breast cancer tumorsPrimary breast lesionsPrimary outcome measureSoft tissueNegative breast cancerLow positivity rateBreast cancer tumorsBone metastasesFoundation MedicineLymph nodesPD-L1Spearman correlation coefficientPD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expressionThe Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation
Taube JM, Akturk G, Angelo M, Engle EL, Gnjatic S, Greenbaum S, Greenwald NF, Hedvat CV, Hollmann TJ, Juco J, Parra ER, Rebelatto MC, Rimm DL, Rodriguez-Canales J, Schalper KA, Stack EC, Ferreira CS, Korski K, Lako A, Rodig SJ, Schenck E, Steele KE, Surace MJ, Tetzlaff MT, von Loga K, Wistuba II, Bifulco CB, . The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation. Journal For ImmunoTherapy Of Cancer 2020, 8: e000155. PMID: 32414858, PMCID: PMC7239569, DOI: 10.1136/jitc-2019-000155.Peer-Reviewed Original ResearchConceptsMultiplex immunohistochemistryImmune cell subsetsImmunotherapy of cancerRoutine clinical practiceMultiplex immunofluorescence analysisDigital spatial profilingMIF assayTask ForceTreatment of cancerCell subsetsPractice guidelinesBest practice guidelinesAcademic centersClinical practiceImmune systemTumor microenvironmentImmunohistochemistryTumor cellsBiomarker studiesCancer statementsChromogenic immunohistochemistryImmunotherapyImmunofluorescence analysisConsecutive stainingCancerDigital quantitative assessment of PD-L1 using digital spatial profiling
Gupta S, Zugazagoitia J, Martinez-Morilla S, Fuhrman K, Rimm DL. Digital quantitative assessment of PD-L1 using digital spatial profiling. Laboratory Investigation 2020, 100: 1311-1317. PMID: 32249818, PMCID: PMC7502436, DOI: 10.1038/s41374-020-0424-5.Peer-Reviewed Original ResearchConceptsTissue microarrayPD-L1Digital spatial profilingDeath 1 ligand 1 expressionPD-L1 immunohistochemistry assaysDigital quantitative assessmentDigital Spatial ProfilerLigand 1 expressionPD-L1 assaysCompanion diagnostic testingCell linesImmune therapyPredictive markerImmune cellsImmunohistochemistry assaysQuantitative immunohistochemistryUS FoodDrug AdministrationDiagnostic testingImmunohistochemistryNCounter platformTumor cellsDifferent scoring methodsMultiple studiesDifferent antibodiesImmune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapy
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 outcomesHigh-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkersReanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, Roden AC, Hirsch FR, Wistuba II, Pusztai L. Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer. Breast Cancer Research 2019, 21: 72. PMID: 31196152, PMCID: PMC6567382, DOI: 10.1186/s13058-019-1156-6.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune cell PD-L1 expressionLung cancerImmune cellsTriple-negative breast cancerEasy scoring methodCompanion diagnostic testsPD-L1Immune therapyBreast cancerImmunohistochemical testsBetter outcomesLarger studyTumor cellsDiagnostic testsCancerExpression findingsCellsExpressionPoor agreementScoring methodTherapyTrialsA Multi-Institutional Study to Evaluate Automated Whole Slide Scoring of Immunohistochemistry for Assessment of Programmed Death-Ligand 1 (PD-L1) Expression in Non–Small Cell Lung Cancer
Taylor CR, Jadhav AP, Gholap A, Kamble G, Huang J, Gown A, Doshi I, Rimm DL. A Multi-Institutional Study to Evaluate Automated Whole Slide Scoring of Immunohistochemistry for Assessment of Programmed Death-Ligand 1 (PD-L1) Expression in Non–Small Cell Lung Cancer. Applied Immunohistochemistry & Molecular Morphology 2019, 27: 263-269. PMID: 30640753, DOI: 10.1097/pai.0000000000000737.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerImmune cellsTumor cellsLin's concordance correlation coefficientLung cancerProgrammed Death Ligand 1 ExpressionDako Link 48 platformDeath ligand 1 (PD-L1) expressionNon-small cell lung carcinomaPD-L1 expressionPD-L1 immunohistochemistryImmune cell populationsImmune cell expressionCell lung carcinomaCell scoringMulti-institutional studyConcordance correlation coefficientImage analysis scoresPD-L1Cell positivityLung carcinomaPatient managementSlide scoringCell expression
2018
Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement
Johnson DB, Nixon MJ, Wang Y, Wang DY, Castellanos E, Estrada MV, Ericsson-Gonzalez PI, Cote CH, Salgado R, Sanchez V, Dean PT, Opalenik SR, Schreeder DM, Rimm DL, Kim JY, Bordeaux J, Loi S, Horn L, Sanders ME, Ferrell PB, Xu Y, Sosman JA, Davis RS, Balko JM. Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement. JCI Insight 2018, 3: e120360. PMID: 30568030, PMCID: PMC6338319, DOI: 10.1172/jci.insight.120360.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, NeutralizingAntigens, CDBreast NeoplasmsCD4-Positive T-LymphocytesCell Line, TumorHistocompatibility Antigens Class IIHLA-DR AntigensHumansImmunotherapyKiller Cells, NaturalLigandsLymphocyte Activation Gene 3 ProteinMiceProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellReceptors, Cell SurfaceT-LymphocytesTumor MicroenvironmentConceptsMHC-II expressionT cellsAnti-PD-1 therapyTumor cellsPD-1 pathwayTumor-intrinsic factorsPD-1-targeted immunotherapiesMHC-II receptorsDurable responsesPD-1Immune activationImmunotherapy targetPreclinical modelsLAG-3TumorsUnique patternMHCEnhanced expressionInhibitory functionAdaptive resistanceNovel inhibitory functionImmunotherapyPatientsContext-dependent mechanismsCellsAn international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer
Rimm DL, Leung SCY, McShane LM, Bai Y, Bane AL, Bartlett JMS, Bayani J, Chang MC, Dean M, Denkert C, Enwere EK, Galderisi C, Gholap A, Hugh JC, Jadhav A, Kornaga EN, Laurinavicius A, Levenson R, Lima J, Miller K, Pantanowitz L, Piper T, Ruan J, Srinivasan M, Virk S, Wu Y, Yang H, Hayes DF, Nielsen TO, Dowsett M. An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer. Modern Pathology 2018, 32: 59-69. PMID: 30143750, DOI: 10.1038/s41379-018-0109-4.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientBreast cancerBreast Cancer Working GroupAssessment of Ki67Pre-specified analysisCancer Working GroupInternational multicenter studyMulticenter studySubsequent clinical validationInternational Ki67Biopsy sectionsClinical valueBiomarker Ki67Breast tumorsKi67 immunohistochemistryEvaluation of reproducibilityKi67Clinical validationTumor cellsObserved intraclass correlation coefficientScoring methodCorrelation coefficientKi67 scoringMaximum scoreCancer
2017
PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors
Kluger HM, Zito CR, Turcu G, Baine M, Zhang H, Adeniran A, Sznol M, Rimm DL, Kluger Y, Chen L, Cohen JV, Jilaveanu LB. PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clinical Cancer Research 2017, 23: 4270-4279. PMID: 28223273, PMCID: PMC5540774, DOI: 10.1158/1078-0432.ccr-16-3146.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionRenal cell carcinomaPD-1 inhibitorsCell carcinomaImmune-infiltrating cellsMelanoma patientsPD-L1Tumor cellsTumor typesTumor-associated inflammatory cellsCTLA-4 inhibitorsCell lung cancerRenal cell carcinoma cellsHigh response rateClin Cancer ResCell linesMelanoma tumor cellsPD-1Multivariable analysisNSCLC specimensInflammatory cellsLung cancerTissue microarrayResponse rateA Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non–Small Cell Lung Cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, Fujimoto J, Yu H, Anders R, Kowalewski A, Rivard C, Rehman J, Batenchuk C, Burns V, Hirsch FR, Wistuba II. A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non–Small Cell Lung Cancer. JAMA Oncology 2017, 3: 1051-1058. PMID: 28278348, PMCID: PMC5650234, DOI: 10.1001/jamaoncol.2017.0013.Peer-Reviewed Original ResearchConceptsPD-L1 expressionNon-small cell lung cancerDako Link 48 platformIntraclass correlation coefficientCell lung cancerImmune cellsPD-L1Tumor cellsSP142 antibodyLung cancerAnti-programmed cell death 1Less PD-L1 expressionCell death ligand 1Tumour cell assessmentPD-L1 antibodiesDeath ligand 1Cell death 1Cell scoringOwn scoring systemSerial histologic sectionsSP142 assayL1 therapyDeath-1Laboratory-developed testsPatient responseP3.02c-067 Validation of PD-L1 Expression on Circulating Tumor Cells in Lung Cancer Topic: IT Biomarkers
Pircher T, Rimm D, Arnold L, Singh V. P3.02c-067 Validation of PD-L1 Expression on Circulating Tumor Cells in Lung Cancer Topic: IT Biomarkers. Journal Of Thoracic Oncology 2017, 12: s1316-s1317. DOI: 10.1016/j.jtho.2016.11.1862.Peer-Reviewed Original Research
2016
Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer
Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL. Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Modern Pathology 2016, 30: 340-349. PMID: 27834350, PMCID: PMC5334264, DOI: 10.1038/modpathol.2016.186.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPD-L1Immune cellsImmune cell PD-L1 expressionNon-small cell lung cancerNon-small cell lung cancer (NSCLC) casesCell lung cancer casesTumor cellsPD-L1 assessmentStromal immune cellsPD-L1 positivityCell lung cancerLung cancer patientsLung cancer casesRepresentative tumor areasPathologist scoresLikelihood of responseConcordance correlation coefficientRabbit monoclonal antibodyIntraclass correlation coefficientCancer patientsLung cancerImmunohistochemistry slidesCancer casesTumor tissue
2015
Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies
Jeon YJ, Khelifa S, Ratnikov B, Scott DA, Feng Y, Parisi F, Ruller C, Lau E, Kim H, Brill LM, Jiang T, Rimm DL, Cardiff RD, Mills GB, Smith JW, Osterman AL, Kluger Y, Ronai Z. Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies. Cancer Cell 2015, 27: 354-369. PMID: 25759021, PMCID: PMC4356903, DOI: 10.1016/j.ccell.2015.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Transport System AAmino Acid Transport System ASCAnimalsAntineoplastic AgentsApoptosisAutophagyBreast NeoplasmsCitric Acid CycleDNA-Binding ProteinsEndoplasmic ReticulumEndoplasmic Reticulum StressFemaleHumansMice, Inbred BALB CMice, Inbred C57BLMice, NudeMinor Histocompatibility AntigensPaclitaxelProteolysisSignal TransductionTOR Serine-Threonine KinasesUbiquitinationUbiquitin-Protein LigasesConceptsBreast cancerPyMT mammary tumorsTCA cycle componentsBreast cancer responseMDA-MB-231 cellsSLC1A5 expressionMammary tumorsCancer responseGlutamine dependencePositive prognosisER stressCell deathAltered metabolismTumor cellsCarrier proteinPaclitaxel responsivenessGln uptakeChemotherapyCycle componentsRegulationExpressionUbiquitinationCellsPrognosis