2023
Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment
Chiorazzi M, Martinek J, Krasnick B, Zheng Y, Robbins K, Qu R, Kaufmann G, Skidmore Z, Juric M, Henze L, Brösecke F, Adonyi A, Zhao J, Shan L, Sefik E, Mudd J, Bi Y, Goedegebuure S, Griffith M, Griffith O, Oyedeji A, Fertuzinhos S, Garcia-Milian R, Boffa D, Detterbeck F, Dhanasopon A, Blasberg J, Judson B, Gettinger S, Politi K, Kluger Y, Palucka K, Fields R, Flavell R. Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment. Journal For ImmunoTherapy Of Cancer 2023, 11: e006921. PMID: 37487666, PMCID: PMC10373695, DOI: 10.1136/jitc-2023-006921.Peer-Reviewed Original ResearchConceptsHuman tumor microenvironmentTumor microenvironmentTumor-immune interactionsSolid tumorsAdaptive immune activationAdaptive immune populationsIndividual tumor microenvironmentsPatient's hematopoietic systemPatient-derived xenograft tissuesVascular endothelial growth factorBone marrow hematopoietic stemBone marrow aspiratePreclinical drug testingEndothelial growth factorHematopoietic systemAutologous tumorPDX modelingPDX miceImmune activationImmune populationsMarrow aspiratesAutologous systemIndividual patientsLittermate controlsPreclinical predictions
2022
Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growthTranscriptional profiling of macrophages in situ in metastatic melanoma reveals localization-dependent phenotypes and function
Martinek J, Lin J, Kim KI, Wang VG, Wu TC, Chiorazzi M, Boruchov H, Gulati A, Seeniraj S, Sun L, Marches F, Robson P, Rongvaux A, Flavell RA, George J, Chuang JH, Banchereau J, Palucka K. Transcriptional profiling of macrophages in situ in metastatic melanoma reveals localization-dependent phenotypes and function. Cell Reports Medicine 2022, 3: 100621. PMID: 35584631, PMCID: PMC9133468, DOI: 10.1016/j.xcrm.2022.100621.Peer-Reviewed Original ResearchConceptsMonocytes/macrophagesDendritic cellsMetastatic melanomaMelanoma cellsMetastatic cutaneous melanomaRegulation of toleranceSpecific transcriptional signatureTranscriptional profilingGene setsLaser capture microdissectionCell-based therapiesTranscriptional signatureCutaneous melanomaDC functionPatient outcomesMetastatic cancerTumor nestsTCGA cohortImmune functionCandidate biomarkersCD14Stromal macrophagesTumor siteTherapeutic opportunitiesAntigen capture
2017
No Oxygen? No Glucose? No Problem: Fatty Acid Catabolism Enhances Effector CD8+ TILs
Bailis W, Shyer JA, Chiorazzi M, Flavell RA. No Oxygen? No Glucose? No Problem: Fatty Acid Catabolism Enhances Effector CD8+ TILs. Cancer Cell 2017, 32: 280-281. PMID: 28898693, PMCID: PMC6939383, DOI: 10.1016/j.ccell.2017.08.013.Peer-Reviewed Original Research
2013
Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma
Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM. Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3943-3948. PMID: 23431138, PMCID: PMC3593917, DOI: 10.1073/pnas.1217271110.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisBase SequenceCaenorhabditis elegansCaenorhabditis elegans ProteinsCaspasesCell Line, TumorEnzyme ActivationF-Box ProteinsHEK293 CellsHumansLymphomaLymphoma, Large B-Cell, DiffuseMolecular Sequence DataMutation, MissenseProto-Oncogene Proteins c-bcl-2Repressor ProteinsRNA, MessengerRNA, NeoplasmSequence Homology, Amino AcidConceptsCED-9Cell deathCaenorhabditis elegansDRE-1Caspase CED-3Control cell deathApoptotic cell deathRegulators of apoptosisEGL-1CED-3Cell fateHuman diffuse large B-cell lymphomaHuman proteinsCaspase activationFBXO10BCL2 proteinElegansProteinHuman malignanciesHuman lymphomasAlternative mechanismApoptosisActivationBH3Regulator
2009
Characterization of early stages of human B cell development by gene expression profiling
Hystad M, Myklebust J, Bø T, Sivertsen E, Rian E, Forfang L, Munthe E, Rosenwald A, Chiorazzi M, Jonassen I, Staudt L, Smeland E. Characterization of early stages of human B cell development by gene expression profiling. The Journal Of Immunology 2009, 182: 5882-5882. DOI: 10.4049/jimmunol.0990031.Peer-Reviewed Original Research
2007
Characterization of Early Stages of Human B Cell Development by Gene Expression Profiling
Hystad ME, Myklebust JH, Bø TH, Sivertsen EA, Rian E, Forfang L, Munthe E, Rosenwald A, Chiorazzi M, Jonassen I, Staudt LM, Smeland EB. Characterization of Early Stages of Human B Cell Development by Gene Expression Profiling. The Journal Of Immunology 2007, 179: 3662-3671. PMID: 17785802, DOI: 10.4049/jimmunol.179.6.3662.Peer-Reviewed Original ResearchConceptsHuman B cell developmentB cell developmentGene expression profilingCell developmentTranscription factorsExpression profilingHemopoietic stem cellsLineage-associated transcription factorsInteresting expression patternsStem cellsMyeloid-associated genesExpression of genesAdult bone marrowFunctional assignmentImmature B cellsKey genesCDNA microarrayGene setsExpression patternsVDJ recombinationUnknown roleB-lymphoid cellsGenesB cellsRNA amplificationTiming of the onset of a developmental cell death is controlled by transcriptional induction of the C. elegans ced-3 caspase-encoding gene
Maurer CW, Chiorazzi M, Shaham S. Timing of the onset of a developmental cell death is controlled by transcriptional induction of the C. elegans ced-3 caspase-encoding gene. Development 2007, 134: 1357-1368. PMID: 17329362, DOI: 10.1242/dev.02818.Peer-Reviewed Original ResearchConceptsCED-3 caspaseCell deathEGL-1Animal developmentTranscriptional inductionCed-9/BclCED-4/ApafTemporal controlPAL-1Such temporal regulationC. elegans homologCell death onsetDevelopmental expression patternsDevelopmental cell deathCell-specific deathEgl-1 expressionCED-4CED-3CED-9Transcriptional regulationSomatic cellsTemporal regulationPromoter sitesExpression patternsTranscriptionPoint mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival
Wiestner A, Tehrani M, Chiorazzi M, Wright G, Gibellini F, Nakayama K, Liu H, Rosenwald A, Muller-Hermelink HK, Ott G, Chan WC, Greiner TC, Weisenburger DD, Vose J, Armitage JO, Gascoyne RD, Connors JM, Campo E, Montserrat E, Bosch F, Smeland EB, Kvaloy S, Holte H, Delabie J, Fisher RI, Grogan TM, Miller TP, Wilson WH, Jaffe ES, Staudt LM. Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival. Blood 2007, 109: 4599-4606. PMID: 17299095, PMCID: PMC1885523, DOI: 10.1182/blood-2006-08-039859.Peer-Reviewed Original Research
2006
Characterization of Early Human B Cell Development by Gene Expression Profiling.
Hystad M, Bo T, Rian E, Myklebust J, Sivertsen E, Forfang L, Chiorazzi M, Rosenwald A, Jonassen I, Staudt L, Smeland E. Characterization of Early Human B Cell Development by Gene Expression Profiling. Blood 2006, 108: 1352. DOI: 10.1182/blood.v108.11.1352.1352.Peer-Reviewed Original ResearchB cell developmentHematopoietic stem cellsHuman B cell developmentGene expression profilingGene expressionFluorescence-activated cell sortingHigh expression levelsImmature B cellsGene OntologyExpression profilingCell developmentB cell lineage commitmentCell populationsTranscription factor E2AEarly B cell developmentExpression levelsExpression of genesProgenitor B cellsPro-B CellsSubsequent fluorescence-activated cell sortingAdult human bone marrowB lineage cellsGene pairsRecombination genesLineage commitment
2005
Cyclin D1–negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling
Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Müller-Hermelink H, Campo E, Gascoyne RD, Staudt LM, Chan C. Cyclin D1–negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 2005, 106: 4315-4321. PMID: 16123218, PMCID: PMC1895253, DOI: 10.1182/blood-2005-04-1753.Peer-Reviewed Original Research
2004
Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune Cells
Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan W, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM. Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune Cells. New England Journal Of Medicine 2004, 351: 2159-2169. PMID: 15548776, DOI: 10.1056/nejmoa041869.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiopsyDendritic CellsFemaleFollow-Up StudiesGene ExpressionGene Expression ProfilingHumansLymphocytes, Tumor-InfiltratingLymphoma, FollicularMacrophagesMaleMiddle AgedMultivariate AnalysisOligonucleotide Array Sequence AnalysisPrognosisProportional Hazards ModelsSurvival AnalysisConceptsLength of survivalImmune cellsFollicular lymphomaMolecular predictorsTumor-Infiltrating Immune CellsClinical prognostic variablesNonmalignant immune cellsUntreated follicular lymphomaTumor biopsy specimensPrediction of survivalMolecular featuresGene expression signaturesMedian lengthSurvival predictorsBiopsy specimensPrognostic variablesPatientsGene expression profilesFlow cytometryGene expression profilingLymphomaSurvivalDiagnosisIndividual genesExpression patterns
2003
Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma
Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P, Gascoyne RD, Chan WC, Zhao T, Haioun C, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Campo E, Montserrat E, Lopez-Guillermo A, Ott G, Muller-Hermelink HK, Connors JM, Braziel R, Grogan TM, Fisher RI, Miller TP, LeBlanc M, Chiorazzi M, Zhao H, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Staudt LM. Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma. Journal Of Experimental Medicine 2003, 198: 851-862. PMID: 12975453, PMCID: PMC2194208, DOI: 10.1084/jem.20031074.Peer-Reviewed Original ResearchMeSH KeywordsAdultChromosomes, Human, Pair 19Diagnosis, DifferentialGene Expression ProfilingHodgkin DiseaseHumansLymphoma, B-CellLymphoma, Large B-Cell, DiffuseMediastinal NeoplasmsMiddle AgedMolecular Diagnostic TechniquesOligonucleotide Array Sequence AnalysisSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsGene expressionHodgkin's lymphoma cellsGenomic lociNeighboring genesMolecular diagnosisPMBL patientsPrimary mediastinal B-cell lymphomaLymphoma cellsHodgkin's lymphoma cell linesLymphoma cell linesDiffuse large B-cell lymphomaDevelopment of therapiesGenesT cell activationPrecise molecular diagnosisCell linesB-cell lymphomaMediastinal B-cell lymphomaLarge B-cell lymphomaCell activationCell lymphomaExpressionHodgkin's lymphomaDLBCL patientsCellsThe proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma
Rosenwald A, Wright G, Wiestner A, Chan C, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 2003, 3: 185-197. PMID: 12620412, DOI: 10.1016/s1535-6108(03)00028-x.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation FactorsAdultAgedAged, 80 and overAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCyclin D1Cyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsFemaleGene Expression ProfilingGenes, NeoplasmHumansLymphoma, Mantle-CellMaleMiddle AgedNeoplasm ProteinsPrognosisProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, NeoplasmSurvival RateTumor Suppressor Protein p53Tumor Suppressor ProteinsUntranslated RegionsConceptsMantle cell lymphoma