2023
Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy
Martinez-Morilla S, Moutafi M, Fernandez A, Jessel S, Divakar P, Wong P, Garcia-Milian R, Schalper K, Kluger H, Rimm D. Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy. OncoImmunology 2023, 12: 2260618. PMID: 37781235, PMCID: PMC10540659, DOI: 10.1080/2162402x.2023.2260618.Peer-Reviewed Original ResearchConceptsDigital spatial profilingImmune checkpoint inhibitor therapyShorter progression-free survivalQuantitative immunofluorescenceCheckpoint inhibitor therapyProgression-free survivalMetastatic melanoma patientsPre-treatment specimensIndependent validation cohortMetastatic melanoma casesAdjuvant settingNanoString GeoMxMultivariable adjustmentAdverse eventsImmunotherapy cohortInhibitor therapyPD-L1Immune markersMelanoma patientsUnivariable analysisValidation cohortImmune cellsMelanoma casesMultiplex immunofluorescenceCD95 expressionSpatial 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
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 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 concordance
2021
Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study
Yaghoobi V, Moutafi M, Aung TN, Pelekanou V, Yaghoubi S, Blenman K, Ibrahim E, Vathiotis IA, Shafi S, Sharma A, O’Meara T, Fernandez AI, Pusztai L, Rimm DL. Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study. Breast Cancer Research 2021, 23: 113. PMID: 34906209, PMCID: PMC8670126, DOI: 10.1186/s13058-021-01493-w.Peer-Reviewed Original ResearchConceptsNegative breast cancerT cellsTumor microenvironmentAA patientsImmune cellsAA tumorsBreast cancerPurposeTriple-negative breast cancerAfrican AmericansTriple-negative breast cancerCase-control studySignificant differencesActivated T cellsImmunologic biomarkersPD-L1Lymphocytic infiltrationLymphoid infiltrationImmune microenvironmentControl cohortTNBC tumorsMyeloid markersQuantitative immunofluorescenceMean expression levelPatientsTNBCInterplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
Zerdes I, Simonetti M, Matikas A, Harbers L, Acs B, Boyaci C, Zhang N, Salgkamis D, Agartz S, Moreno-Ruiz P, Bai Y, Rimm DL, Hartman J, Mezheyeuski A, Bergh J, Crosetto N, Foukakis T. Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study. Npj Breast Cancer 2021, 7: 144. PMID: 34799582, PMCID: PMC8604966, DOI: 10.1038/s41523-021-00352-3.Peer-Reviewed Original ResearchMultiplexed fluorescent immunohistochemistryPhase II trialII trialEarly breast cancer patientsSomatic copy number alterationsCopy number alterationsEarly breast cancerBreast cancer patientsAbundant immune cellsImmune cell compositionParaffin-embedded tissue samplesNumber alterationsImmune profilePD-1PD-L1Immune profilingLymphocytic infiltrationCancer patientsImmune cellsBreast cancerT cellsLarge cohortFluorescent immunohistochemistryTissue samplesPathological samplesInterobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group
Van Bockstal MR, Cooks M, Nederlof I, Brinkhuis M, Dutman A, Koopmans M, Kooreman L, van der Vegt B, Verhoog L, Vreuls C, Westenend P, Kok M, van Diest PJ, Nauwelaers I, Laudus N, Denkert C, Rimm D, Siziopikou KP, Ely S, Zardavas D, Roberts M, Floris G, Hartman J, Acs B, Peeters D, Bartlett JMS, Dequeker E, Salgado R, Giudici F, Michiels S, Horlings H, van Deurzen CHM. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group. Cancers 2021, 13: 4910. PMID: 34638394, PMCID: PMC8507620, DOI: 10.3390/cancers13194910.Peer-Reviewed Original ResearchTumor-Infiltrating LymphocytesPD-L1 statusTNBC metastasisPrimary TNBCInterobserver agreementInternational Immuno-Oncology Biomarker Working GroupTriple-negative breast cancerBiomarker Working GroupBreast cancer benefitIndividual patient levelChance of treatmentCancer benefitDistant metastasisMetastatic TNBCImmune cellsSame pathologistPatient levelBreast cancerAnatomic localizationConsensus diagnosisMetastatic specimensMetastasisInter-pathologist agreementTNBCModerate agreementPutting 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 ResearchQuantitative 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
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 expressionDigital 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
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
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
2017
A 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 response
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