2020
Quantitative analysis of CMTM6 expression in tumor microenvironment in metastatic melanoma and association with outcome on immunotherapy
Martinez-Morilla S, Zugazagoitia J, Wong PF, Kluger HM, Rimm DL. Quantitative analysis of CMTM6 expression in tumor microenvironment in metastatic melanoma and association with outcome on immunotherapy. OncoImmunology 2020, 10: 1864909. PMID: 33457084, PMCID: PMC7781756, DOI: 10.1080/2162402x.2020.1864909.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-L1CMTM6 expressionControl patientsLonger survivalTissue microarrayQuantitative immunofluorescenceEffectiveness of immunotherapyMetastatic melanoma patientsDeath ligand 1Like MARVEL transmembrane domainCancer Genome Atlas (TCGA) databaseExpression of CMTM6MARVEL transmembrane domainExpression of mRNAChemokine-like factorICI treatmentCheckpoint inhibitorsPretreatment biopsiesCD68 markersImmune compartmentMultivariable analysisMelanoma patientsImmune-related proteinsPredictive factors
2019
An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma
Acs B, Ahmed FS, Gupta S, Wong P, Gartrell RD, Sarin Pradhan J, Rizk EM, Gould Rothberg BE, Saenger YM, Rimm DL. An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma. Nature Communications 2019, 10: 5440. PMID: 31784511, PMCID: PMC6884485, DOI: 10.1038/s41467-019-13043-2.Peer-Reviewed Original ResearchConceptsOpen sourceOpen source softwareSource softwareTIL scoreTraining setDisease-specific overall survivalHigh TIL scorePoor prognosis cohortsSubset of patientsAlgorithmIndependent prognostic markerBroad adoptionAssessment of tumorOverall survivalFavorable prognosisMelanoma patientsMultivariable analysisValidation cohortIndependent associationPrognostic markerSeparate patientsPrognostic variablesIndependent cohortRetrospective collectionMelanomaMultiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman K, Zelterman D, Kluger HM, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma. Clinical Cancer Research 2019, 25: 2442-2449. PMID: 30617133, PMCID: PMC6467753, DOI: 10.1158/1078-0432.ccr-18-2652.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkersBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingROC CurveT-Lymphocyte SubsetsConceptsCell countTIL activationQuantitative immunofluorescenceLymphocytic infiltrationMelanoma patientsMetastatic melanomaAnti-PD-1 responseAnti-PD-1 therapyCell death 1 (PD-1) inhibitionAbsence of immunotherapyDeath-1 (PD-1) inhibitionDisease control rateProgression-free survivalCD8 cell countsTumor-Infiltrating LymphocytesNew predictive biomarkersWhole tissue sectionsRECIST 1.1Progressive diseaseDurable responsesObjective responsePartial responseImmunotherapy outcomesLymphocyte profilesMultivariable analysis
2017
Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer
Carvajal-Hausdorf DE, Mani N, Velcheti V, Schalper KA, Rimm DL. Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2017, 5: 81. PMID: 29037255, PMCID: PMC5644103, DOI: 10.1186/s40425-017-0285-7.Peer-Reviewed Original ResearchConceptsHormone receptor-positive breast cancerReceptor-positive breast cancerIDO1 expressionBreast cancerIndependent negative prognostic markerB cell infiltrationImmune suppressive pathwaysAdvanced solid tumorsTumor-infiltrating lymphocytesT cell responsesClinico-pathological featuresClinico-pathological characteristicsProportional hazards modelNegative prognostic markerDegradation of tryptophanMann-Whitney testFoxp3 levelsIDO1 blockadeIDO1 levelsEffector CD4Durable responsesOverall survivalImmune toleranceMultivariable analysisPrognostic markerPD-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 rate
2015
Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer
Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, Herbst RS, Rimm DL. Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer. Journal Of The National Cancer Institute 2015, 107: dju435. PMID: 25650315, PMCID: PMC4565530, DOI: 10.1093/jnci/dju435.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD20Carcinoma, Non-Small-Cell LungCD3 ComplexCD8 AntigensConfounding Factors, EpidemiologicFluorescent DyesHumansIndolesKaplan-Meier EstimateLung NeoplasmsLymphocytes, Tumor-InfiltratingMicroscopy, FluorescencePredictive Value of TestsRetrospective StudiesT-Lymphocytes, CytotoxicConceptsTumor-infiltrating lymphocytesLevels of CD3TIL subtypesMultivariable analysisTumor sizeLonger survivalAssociation of TILsLevel of TILsNon-small cell lung cancerNon-small cell lung cancer samplesLocal immune effectsClinico-pathologic characteristicsImmune checkpoint inhibitorsCell lung cancerCell lung cancer samplesLung cancer samplesDifferent tumor compartmentsObjective measurementsElevated CD3High CD20TIL markersTIL subpopulationsCheckpoint inhibitorsSmoking historyHistology type
2013
Quantitative Ki-67 score as predictive of response to neoadjuvant chemotherapy in breast cancer.
Brown J, Lannin D, Killelea B, DiGiovanna M, Rimm D. Quantitative Ki-67 score as predictive of response to neoadjuvant chemotherapy in breast cancer. Journal Of Clinical Oncology 2013, 31: 1085-1085. DOI: 10.1200/jco.2013.31.15_suppl.1085.Peer-Reviewed Original ResearchKi-67 expressionPathological complete responseNeoadjuvant chemotherapyKi-67Consecutive invasive breast cancer patientsAQUA scoreInvasive breast cancer patientsAdditional survival benefitBreast cancer patientsKi-67 levelsPre-surgical biopsyKi-67 scoreLikelihood of responseMIB-1 antibodyPrediction of responseNeoadjuvant therapyComplete responseNodal statusSurvival benefitER statusIndependent predictorsMultivariable analysisAdvanced tumorsTumor sizeCancer patientsEffect of PDL-1 expression on prognosis in head and neck squamous cell carcinoma.
Vasilakopoulou M, Velcheti V, Rampias T, Sasaki C, Rimm D, Fountzilas G, Psyrri A. Effect of PDL-1 expression on prognosis in head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2013, 31: 6012-6012. DOI: 10.1200/jco.2013.31.15_suppl.6012.Peer-Reviewed Original ResearchPDL-1 expressionPDL-1Prognostic significanceT cellsMultivariate Cox proportional hazards modelCox proportional hazards modelNeck squamous cell carcinomaDeath-1 receptorFavorable clinical outcomeKaplan-Meier methodInduces tumor regressionSquamous cell carcinomaHNSCC tissue microarrayLog-rank testProportional hazards modelProtein expression levelsImproved DFSEfficacy outcomesImmunotherapeutic approachesClinical outcomesMultivariable analysisEntire cohortCell carcinomaCancer patientsFavorable outcomeHigh Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer
Liu M, Mor G, Cheng H, Xiang X, Hui P, Rutherford T, Yin G, Rimm DL, Holmberg J, Alvero A, Silasi DA. High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer. Reproductive Sciences 2013, 20: 605-615. PMID: 23171677, PMCID: PMC3635069, DOI: 10.1177/1933719112461183.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnalysis of VarianceBiomarkers, TumorCarcinoma, Ovarian EpithelialDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmFemaleHumansHyaluronan ReceptorsKaplan-Meier EstimateKeratin-19Middle AgedMultivariate AnalysisNeoplasm Recurrence, LocalNeoplasm StagingNeoplasms, Glandular and EpithelialNeoplastic Stem CellsOvarian NeoplasmsProportional Hazards ModelsRetrospective StudiesRisk FactorsTime FactorsTreatment OutcomeConceptsPutative ovarian cancer stem cellsOvarian cancer stem cellsProgression-free intervalCancer stem cellsRecurrent epithelial ovarian cancerShorter disease-free intervalShorter progression-free intervalDisease-free intervalResidual tumor volumeEpithelial ovarian cancerLog-rank testEpithelial ovarian cancer cellsIndependent significant predictorsAdvanced stage EOCOvarian cancer cellsStem cellsMean followObstetrics stageUnivariable analysisClinicopathologic featuresMultivariable analysisRetrospective studyPrognostic valueOvarian cancerTumor volume
2009
Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer
Nadler Y, González AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Annals Of Oncology 2009, 21: 466-473. PMID: 19717535, PMCID: PMC2826097, DOI: 10.1093/annonc/mdp346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularFemaleFluorescent Antibody TechniqueFollow-Up StudiesGRB7 Adaptor ProteinHumansImage Processing, Computer-AssistedMiddle AgedPrognosisReceptor, ErbB-2Survival RateTissue Array AnalysisTumor Cells, CulturedYoung AdultConceptsHER2/neuBreast cancerPrognostic markerHER2/neu-positive breast cancerGRB7 expressionHigh HER2/neuNeu-positive breast cancerHER2/neu overexpressionPrimary breast cancerBreast cancer patientsIndependent prognostic markerNode-positive subsetValuable prognostic markerProtein 7Cy5-conjugated antibodiesMultivariable analysisWorse prognosisEntire cohortCancer patientsNeu overexpressionTissue microarrayTherapeutic targetCancerNeuPatientsTissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis
Rothberg BE, Bracken MB, Rimm DL. Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis. Journal Of The National Cancer Institute 2009, 101: 452-474. PMID: 19318635, PMCID: PMC2720709, DOI: 10.1093/jnci/djp038.Peer-Reviewed Original ResearchConceptsCohort studyCutaneous melanomaMelanoma cell adhesion moleculeSystematic reviewEarly-stage cutaneous melanomaPotential prognostic valueMatrix metalloproteinase-2Cell nuclear antigenREMARK criteriaAdjuvant therapyMultivariable analysisREMARK guidelinesRisk stratificationPrognostic valueSurvival outcomesIncomplete adherenceMelanoma outcomesClinical managementImmunohistochemical expressionCell adhesion moleculeInclusion criteriaKi-67Tissue biomarkersClinical practiceMetalloproteinase-2
2008
Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer
Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer. Clinical Cancer Research 2008, 14: 4455-4462. PMID: 18628459, PMCID: PMC5849429, DOI: 10.1158/1078-0432.ccr-07-5268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAurora Kinase BAurora KinasesBiomarkers, TumorBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleHistory, 17th CenturyHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimatePrognosisProtein Serine-Threonine KinasesTissue Array AnalysisConceptsBreast cancerB expressionAurora B expressionBreast tumorsHigh AuroraEarly-stage breast cancerHER-2/neuProgesterone receptor expressionSubset of patientsPopulation of patientsIndependent prognostic markerHigh nuclear gradePrimary breast tumorsCy5-conjugated antibodiesPathologic variablesPrognostic roleMultivariable analysisProspective studyNuclear gradePrognostic markerReceptor expressionClinical developmentPatientsPredictive roleCancerExpression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Research 2008, 10: r35. PMID: 18430249, PMCID: PMC2397537, DOI: 10.1186/bcr1998.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptors, EstrogenReceptors, ProgesteroneTranscription FactorsTreatment OutcomeConceptsNode-positive subsetHER2/neuProgesterone receptorBreast cancerEstrogen receptorBcl-2 expressionBAG-1 expressionImproved survivalBcl-2Anti-apoptotic mediator Bcl-2Breast tumorsSteroid receptor positivitySubset of patientsBAG-1Antihormonal therapyFavorable prognosisReceptor positivityMultivariable analysisPathological variablesEntire cohortPrognostic valuePrognostic markerImproved outcomesLarge cohortClinical development
2007
High HSP90 Expression Is Associated with Decreased Survival in Breast Cancer
Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, Kluger HM. High HSP90 Expression Is Associated with Decreased Survival in Breast Cancer. Cancer Research 2007, 67: 2932-2937. PMID: 17409397, DOI: 10.1158/0008-5472.can-06-4511.Peer-Reviewed Original ResearchConceptsHigh HSP90 expressionBreast cancerHER2/neuHSP90 expressionEstrogen receptorHigh HER2/neuCell linesEarly-stage breast cancerHER2/neu expressionHuman tumorsLymph node involvementPrimary breast cancerSubset of patientsPopulation of patientsIndependent prognostic markerHigh nuclear gradeBreast cancer cell linesBreast cancer progressionCy5-conjugated antibodiesCancer cell linesNode involvementPathologic variablesPrognostic roleMultivariable analysisProspective study
2006
Evaluation of the Prognostic Value of Cellular Inhibitor of Apoptosis Protein in Epithelial Ovarian Cancer Using Automated Quantitative Protein Analysis
Psyrri A, Yu Z, Bamias A, Weinberger PM, Markakis S, Kowalski D, Camp RL, Rimm DL, Dimopoulos MA. Evaluation of the Prognostic Value of Cellular Inhibitor of Apoptosis Protein in Epithelial Ovarian Cancer Using Automated Quantitative Protein Analysis. Cancer Epidemiology Biomarkers & Prevention 2006, 15: 1179-1183. PMID: 16775178, DOI: 10.1158/1055-9965.epi-06-0120.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerOvarian cancerPrognostic valuePaclitaxel-based combination chemotherapyOnly significant prognostic factorAdvanced stage ovarian cancerSignificant prognostic factorsOvarian cancer patientsProtein levelsImportant prognostic biomarkerMean followSurgical debulkingCombination chemotherapyOverall survivalPrognostic factorsClinical outcomesMultivariable analysisEntire cohortCancer patientsPrognostic biomarkerPrognostic variablesMembranous expressionApoptosis proteinSurvival rateCellular inhibitor
2005
Effect of Epidermal Growth Factor Receptor Expression Level on Survival in Patients with Epithelial Ovarian Cancer
Psyrri A, Kassar M, Yu Z, Bamias A, Weinberger PM, Markakis S, Kowalski D, Camp RL, Rimm DL, Dimopoulos MA. Effect of Epidermal Growth Factor Receptor Expression Level on Survival in Patients with Epithelial Ovarian Cancer. Clinical Cancer Research 2005, 11: 8637-8643. PMID: 16361548, DOI: 10.1158/1078-0432.ccr-05-1436.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorOvarian cancerOverall survivalPrognostic valuePlatinum-paclitaxel combination chemotherapyAdvanced stage ovarian cancerDisease-free survivalSignificant prognostic factorsAdverse prognostic indicatorEpithelial ovarian cancerTumor EGFR expressionEGFR expression statusImportant prognostic informationConflicting resultsEpidermal growth factor receptor expression levelsEGFR protein expressionReceptor expression levelsGrowth factor receptorSurgical debulkingCombination chemotherapyPrognostic factorsMultivariable analysisEntire cohortPoor outcomePrognostic indicatorSubcellular Localization and Protein Levels of Cyclin-Dependent Kinase Inhibitor p27 Independently Predict for Survival in Epithelial Ovarian Cancer
Psyrri A, Bamias A, Yu Z, Weinberger PM, Kassar M, Markakis S, Kowalski D, Efstathiou E, Camp RL, Rimm DL, Dimopoulos MA. Subcellular Localization and Protein Levels of Cyclin-Dependent Kinase Inhibitor p27 Independently Predict for Survival in Epithelial Ovarian Cancer. Clinical Cancer Research 2005, 11: 8384-8390. PMID: 16322299, DOI: 10.1158/1078-0432.ccr-05-1270.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCell DifferentiationCohort StudiesCombined Modality TherapyCyclin-Dependent Kinase Inhibitor p27Cystadenocarcinoma, SerousFemaleHumansMiddle AgedNeoplasm StagingNeoplasms, Glandular and EpithelialOvarian NeoplasmsPrognosisSubcellular FractionsSurvival RateTissue Array AnalysisConceptsNuclear p27 expressionOvarian cancerP27 expression levelsOverall survivalP27 expressionPlatinum-paclitaxel combination chemotherapyAdvanced stage ovarian cancerDisease-free survivalSignificant prognostic factorsStage ovarian cancerEpithelial ovarian cancerValuable prognostic biomarkerExpression levelsP27 protein expressionCyclin-dependent kinase inhibitor p27Mean followSurgical debulkingCombination chemotherapyPrognostic factorsMultivariable analysisPrognostic valueImmunohistochemical assessmentPrognostic biomarkerPrognostic variablesImmunofluorescence-based method