2024
Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma
Su D, Schoenfeld D, Ibrahim W, Cabrejo R, Djureinovic D, Baumann R, Rimm D, Khan S, Halaban R, Kluger H, Olino K, Galan A, Clune J. Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma. Journal For ImmunoTherapy Of Cancer 2024, 12: e008646. PMID: 38519058, PMCID: PMC10961546, DOI: 10.1136/jitc-2023-008646.Peer-Reviewed Original ResearchConceptsCTLA-4 expression levelsCancer-associated fibroblastsAssociated with worse survivalExpression of immune checkpointsLAG-3 expressionDesmoplastic melanomaLymphoid aggregatesCTLA-4PD-1Immune checkpointsIntratumoral leukocytesLAG-3Tumor compartmentsWorse survivalCD20+B cellsIncreased expression of immune checkpointsProgrammed cell death protein 1Macrophage/monocyte markerSentinel lymph node positivityCell death protein 1Associated with poor prognosisLymph node positivityDense fibrous stromaPotential prognostic significanceCore of tumors
2021
Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes
Apostolidi M, Vathiotis IA, Muthusamy V, Gaule P, Gassaway BM, Rimm DL, Rinehart J. Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes. Cancer Research 2021, 81: 4346-4359. PMID: 34185676, PMCID: PMC8373815, DOI: 10.1158/0008-5472.can-20-4190.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsBiomarkers, TumorCarrier ProteinsCell Line, TumorCollagenCyclic N-OxidesDrug CombinationsGenome, HumanHumansIndolizinesLamininMCF-7 CellsMembrane ProteinsMiceNeoplasm InvasivenessNeoplasm TransplantationNeoplasmsOxidation-ReductionPhenotypePhosphorylationProtein IsoformsProteoglycansProteomicsPyridazinesPyridinium CompoundsPyrrolesPyruvate KinaseThyroid HormonesTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPyruvate kinase M2TEPP-46Breast cancerAggressive breast cancer cell phenotypesCharacteristic nuclear staining patternAggressive breast cancer subtypeAggressive breast cancer phenotypeBreast cancer cell phenotypeCDK inhibitor dinaciclibCombination of dinaciclibLack of biomarkersEffective therapeutic approachBreast cancer phenotypeBreast cancer subtypesCancer phenotypePhosphorylation of PKM2Cyclin-dependent kinase (CDK) pathwayMouse xenograft modelAggressive cancer phenotypeNuclear staining patternLower survival rateImpaired redox balancePrognostic valueCancer cell phenotype
2020
Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges.
McKean WB, Moser JC, Rimm D, Hu-Lieskovan S. Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges. American Society Of Clinical Oncology Educational Book 2020, 40: e275-e291. PMID: 32453632, DOI: 10.1200/edbk_280571.Peer-Reviewed Original ResearchConceptsHost immune defectsPrecision cancer immunotherapyHealth care burdenCurrent treatment modalitiesSignificant side effectsSustained remissionClinical responseCheckpoint inhibitionImmune defectsRefractory malignanciesCancer immunotherapeuticsClinical benefitPatient survivalCancer immunotherapyPredictive biomarkersTreatment modalitiesCare burdenPatient responseSide effectsTrial designTumor parenchymaClinical useBiomarker developmentBiomarkersMultiple biomarkers
2017
Proof of the quantitative potential of immunofluorescence by mass spectrometry
Toki MI, Cecchi F, Hembrough T, Syrigos KN, Rimm DL. Proof of the quantitative potential of immunofluorescence by mass spectrometry. Laboratory Investigation 2017, 97: 329-334. PMID: 28092364, PMCID: PMC5334147, DOI: 10.1038/labinvest.2016.148.Peer-Reviewed Original Research
2015
Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer
Blume-Jensen P, Berman DM, Rimm DL, Shipitsin M, Putzi M, Nifong TP, Small C, Choudhury S, Capela T, Coupal L, Ernst C, Hurley A, Kaprelyants A, Chang H, Giladi E, Nardone J, Dunyak J, Loda M, Klein EA, Magi-Galluzzi C, Latour M, Epstein JI, Kantoff P, Saad F. Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer. Clinical Cancer Research 2015, 21: 2591-2600. PMID: 25733599, DOI: 10.1158/1078-0432.ccr-14-2603.Peer-Reviewed Original ResearchConceptsBiomarker risk scoreRisk scoreRisk groupsPredictive valueNational Comprehensive Cancer NetworkComprehensive Cancer NetworkCurrent risk stratification systemsIndependent prognostic informationRisk stratification systemProstate cancer aggressivenessRisk classification groupsAccurate risk predictionCoprimary endpointsFavorable pathologyAppropriate therapyCurative therapyRisk stratificationPathologic parametersPrognostic informationProstate biopsyProstate pathologyProstate cancerBlinded studyProstatectomy specimensCancer Network
2014
Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error
Shipitsin M, Small C, Choudhury S, Giladi E, Friedlander S, Nardone J, Hussain S, Hurley AD, Ernst C, Huang YE, Chang H, Nifong TP, Rimm DL, Dunyak J, Loda M, Berman DM, Blume-Jensen P. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error. British Journal Of Cancer 2014, 111: 1201-1212. PMID: 25032733, PMCID: PMC4453845, DOI: 10.1038/bjc.2014.396.Peer-Reviewed Original ResearchMeSH KeywordsActininAgedAlkyl and Aryl TransferasesArea Under CurveBiomarkers, TumorBiopsy, Fine-NeedleCullin ProteinsDNA-Binding ProteinsFollow-Up StudiesHSP70 Heat-Shock ProteinsHumansImage Processing, Computer-AssistedMaleMembrane ProteinsMiddle AgedMitochondrial ProteinsNeoplasm GradingNeoplasm StagingPhosphorylationProstateProstatic NeoplasmsProteomicsRibosomal Protein S6RNA-Binding Protein FUSROC CurveSelection BiasSmad2 ProteinSmad4 ProteinTissue Array AnalysisVoltage-Dependent Anion Channel 1Y-Box-Binding Protein 1ConceptsProstate cancer aggressivenessCancer aggressivenessLarge patient cohortLow Gleason gradePatient cohortTumor microarrayLethal outcomeProstatectomy samplesGleason gradeSignificant overtreatmentBiopsy interpretationProstatectomy tissuePatient samplesBiopsy testsProteomic biomarkersCancer biomarker discoveryExpert pathologistsMarker signaturesTumor heterogeneityBiomarkersAggressivenessProtein biomarkersBiomarker discoveryQuantitative proteomics approachQuantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab
Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer 2014, 14: 326. PMID: 24885187, PMCID: PMC4037428, DOI: 10.1186/1471-2407-14-326.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarboplatinChemotherapy, AdjuvantConnecticutFemaleFluorescent Antibody TechniqueHumansNeoadjuvant TherapyPaclitaxelPhosphorylationProteomicsReceptor, ErbB-2Rhode IslandTime FactorsTrastuzumabTreatment OutcomeConceptsLikelihood of responsePhospho-HER2Nab-paclitaxelPathologic responseHER2 levelsAdvanced HER2-positive breast cancerHER2-positive breast cancerCarboplatin combination therapyPre-surgical settingPreoperative clinical trialSingle-agent trastuzumabPathologic complete responseInitiation of treatmentWeeks of treatmentBreast cancer patientsTumor core biopsiesCore biopsy samplesMonoclonal antibody trastuzumabEvaluable patientsNeoadjuvant regimenNeoadjuvant chemotherapyNeoadjuvant therapyNeoadjuvant treatmentComplete responsePreoperative setting