2023
Development of Chimeric Antigen Receptor (CAR) T Cells Targeting MET in Lymphomas and Solid Tumors
Chen P, Raghunandan R, Müschen M, Katz S. Development of Chimeric Antigen Receptor (CAR) T Cells Targeting MET in Lymphomas and Solid Tumors. Blood 2023, 142: 6805. DOI: 10.1182/blood-2023-186161.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaB-cell lymphomaChimeric antigen receptor T cellsAntigen receptor T cellsLarge B-cell lymphomaReceptor T cellsT cellsLymphoma cell linesHGF/METMET expressionOCI-Ly3CD69 expressionDLBCL cell linesCD19-CARSolid tumorsCell linesAnti-Met monoclonal antibodiesCD19 CAR T cellsNegative diffuse large B-cell lymphomaRefractory B-cell malignanciesLoss of CD19B-cell depletionActivation marker CD69Classic Hodgkin lymphomaJurkat T cellsPD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma
Wartewig T, Daniels J, Schulz M, Hameister E, Joshi A, Park J, Morrish E, Venkatasubramani A, Cernilogar F, van Heijster F, Hundshammer C, Schneider H, Konstantinidis F, Gabler J, Klement C, Kurniawan H, Law C, Lee Y, Choi S, Guitart J, Forne I, Giustinani J, Müschen M, Jain S, Weinstock D, Rad R, Ortonne N, Schilling F, Schotta G, Imhof A, Brenner D, Choi J, Ruland J. PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma. Nature Cancer 2023, 4: 1508-1525. PMID: 37723306, PMCID: PMC10597841, DOI: 10.1038/s43018-023-00635-7.Peer-Reviewed Original ResearchConceptsPD-1T-NHLAP-1 activityT-cell non-Hodgkin lymphomaImmune checkpoint receptor PD-1Cell non-Hodgkin lymphomaCheckpoint receptor PD-1Receptor PD-1Non-Hodgkin lymphomaT-cell lymphomaT-cell malignanciesPrimary patient samplesTractable mouse modelAdvanced diseaseInferior prognosisProtein-1 transcription factorT cellsCell lymphomaMouse modelCell malignanciesATP citrate lyase activityACLY inhibitionPatient samplesTumor suppressive mechanismKey tumor suppressor
2019
Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies
Sadras T, Martin M, Kim-Sing L, Cutler J, Lenz G, Knapp A, Ghergus D, Delmotte F, Schleiss C, Korganow A, Soulas-Sprauel P, Chen Z, Pandey A, Weinstock D, Jumaa H, Meffre E, Martin T, Müschen M. Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies. Blood 2019, 134: 295. DOI: 10.1182/blood-2019-128999.Peer-Reviewed Original ResearchB-cell chronic lymphocytic leukemiaNegative B cell selectionB cellsB-cell malignanciesB cell selectionCo-expressing cellsT cellsBCR-stimulated B cellsZAP70 expressionMultiple B-cell malignanciesLymphoma cellsAutoreactive BCRsCentral tolerance checkpointsCell deathT cell populationsB cell compartmentChronic lymphocytic leukemiaProximity ligation assayB-cell lymphoma cellsMantle cell lymphomaTumor B cellsExpression of ZAP70Human B-cell lymphoma cellsImmature B cellsDevelopment of leukemia
2018
DUSP1/6 Inhibition Reduces Tumor Cells and Activates Immune Response in Chronic Lymphocytic Leukemia
Braun M, Ecker V, Neumayer T, Muschen M, Ruland J, Buchner M. DUSP1/6 Inhibition Reduces Tumor Cells and Activates Immune Response in Chronic Lymphocytic Leukemia. Blood 2018, 132: 2857. DOI: 10.1182/blood-2018-99-117052.Peer-Reviewed Original ResearchPatient-derived peripheral blood mononuclear cellsChronic lymphocytic leukemiaMyeloid-derived suppressor cellsB cell receptorImmunogenic cell deathCLL cellsPrimary CLL cellsB cellsImmune cellsT cellsTreatment optionsImmune responseLymphocytic leukemiaBCI treatmentDonor-derived B cellsAntigen-specific T cell proliferationHematopoietic stem cell transplantationPeripheral blood mononuclear cellsHigh-mobility group box 1 proteinMobility group box 1 proteinCell deathGroup box 1 proteinHyperphosphorylation of ERK1/2Poor-risk diseaseCD8 T cellsNovel BAFF-R CAR T-Cell Therapy for CD19 Antigen-Loss Relapsed B Cell Tumors
Qin H, Dong Z, Wang X, Cheng W, Smith D, Song J, Aldoss I, Muschen M, Forman S, Kwak L. Novel BAFF-R CAR T-Cell Therapy for CD19 Antigen-Loss Relapsed B Cell Tumors. Blood 2018, 132: 1411. DOI: 10.1182/blood-2018-99-117513.Peer-Reviewed Original ResearchCD19 CAR T cellsCAR T cellsCAR T-cell therapyT-cell therapyBAFF-R expressionT cellsB-cell malignanciesAntigen lossB-cell tumorsCell malignanciesClonal B-cell tumorChimeric antigen receptor T cellsAntigen receptor T cellsSame donorCD22 CAR T cellsSurface stainingCD19 antigen lossLoss of CD19Degranulation marker CD107aCells/mouseProgressive tumor growthIFN-γ productionReceptor T cellsSame healthy donorsPatient-derived xenograftsSHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia
Ecker V, Braun M, Neumayer T, Muschen M, Ruland J, Buchner M. SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia. Blood 2018, 132: 894. DOI: 10.1182/blood-2018-99-117053.Peer-Reviewed Original ResearchChronic lymphocytic leukemiaMyeloid-derived suppressor cellsSecondary lymphoid organsImmune cell functionPeripheral bloodCLL cellsLymph nodesMalignant CLL cellsB cellsT cellsImmune responseLymphoid organsLymphocytic leukemiaSmall molecule inhibitorsSHIP1 inhibitionAge-matched healthy donorsAnti-tumor immune responsePharmacological inhibitionCell deathCLL peripheral bloodTreatment-related toxicityImmunoglobulin-producing plasma cellsRegulatory T cellsCell functionCLL cell deathCD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies
Lee J, Kume K, Chen Z, Xiao G, Cosgun K, Chan L, Chen C, Pillai R, Chan W, Forman S, Kwak L, Zammarchi F, Van Berkel P, Weinstock D, Melnick A, Ngo V, Geng H, Luger S, Litzow M, Belot A, Uzel G, McManus M, Paietta E, Meffre E, Muschen M. CD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies. Blood 2018, 132: 776. DOI: 10.1182/blood-2018-99-117553.Peer-Reviewed Original ResearchB cell receptorReceptor chainsB-cell malignanciesNormal B cell developmentT cell receptor signalingB-cell leukemiaHomology-directed repairCell membrane translocationPoor clinical outcomeB cell developmentFeedback regulatorTransplant recipientsNegative feedback regulatorNegative feedback regulationCytoplasmic tailClinical outcomesGene expressionMolecule downstreamCytokine receptor chainsBCR signalingT cellsB cell selectionGenetic mouse modelsProliferation signalsAstra Zeneca
2016
CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies
Lee J, Geng H, Chen Z, Klemm L, Cosgun K, Xiao G, Masouleh B, Hurtz C, Parekh S, Kornblau S, Melnick A, Abbas A, Paietta E, Müschen M. CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies. Blood 2016, 128: 4088. DOI: 10.1182/blood.v128.22.4088.4088.Peer-Reviewed Original ResearchB-cell malignanciesB-cell tumorsB cell receptorPoor clinical outcomeCell tumorsCell malignanciesClinical outcomesCD25 expressionB-cell leukemiaT cellsClinical cohortCell leukemiaTherapeutic targetB cellsRefractory B-cell malignanciesCell receptorExpression levelsMultiple B-cell malignanciesTumor clonesRegulatory T cellsHigh expression levelsDivergent clinical outcomesBCR signalingHuman B-cell malignanciesB-cell lymphoma cells
2001
Evidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions
Küppers R, Bräuninger A, Müschen M, Distler V, Hansmann M, Rajewsky K. Evidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions. Blood 2001, 97: 818-821. PMID: 11157505, DOI: 10.1182/blood.v97.3.818.Peer-Reviewed Original ResearchConceptsHodgkin's diseaseReed-Sternberg cellsHRS cellsT-cell receptor beta rearrangementsCases of HDClassical Hodgkin's diseaseCoexpression of markersCell fusionNumerical chromosomal abnormalitiesUnusual immunophenotypeT cellsRare caseB cellsBeta rearrangementChromosomal abnormalitiesGermline configurationIgH allelesDifferent hematopoietic lineagesDiseaseHodgkinCell generationCellsTCRbeta allelesHematopoietic lineagesImmunoglobulin genes
2000
CD95 ligand expression as a mechanism of immune escape in breast cancer
Müschen M, Moers C, Warskulat U, Even J, Niederacher D, Beckmann M. CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology 2000, 99: 69-77. PMID: 10651943, PMCID: PMC2327134, DOI: 10.1046/j.1365-2567.2000.00921.x.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBreast NeoplasmsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFas Ligand ProteinFas ReceptorFemaleFlow CytometryHumansImmunohistochemistryJurkat CellsLymphocyte CountMembrane GlycoproteinsProtein IsoformsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsBreast cancer cellsT cellsBreast cancerCD95L expressionImmune escapeIFN-gammaCancer cellsJurkat T cellsTumor-infiltrating T cellsCD95L mRNA levelsDepletion of CD4Cultured breast cancer cellsBreast cancer patientsPeripheral blood lymphocytesCD95/CD95L systemBreast cancer cell linesNon-malignant mammary tissuesActivated T cellsCD95 ligand expressionRate of apoptosisBreast cancer sectionsCancer cell linesInteraction of CD95Systemic immunosuppressionCancer patients
1998
Fas LIGAND, TUMOR NECROSIS FACTOR-α EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT REJECTION AND TOLERANCE
Josien R, Müschen M, Gilbert E, Douillard P, Heslan J, Soulillou J, Cuturi M. Fas LIGAND, TUMOR NECROSIS FACTOR-α EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT REJECTION AND TOLERANCE. Transplantation 1998, 66: 887-893. PMID: 9798699, DOI: 10.1097/00007890-199810150-00013.Peer-Reviewed Original ResearchConceptsAllograft rejectionTNF-alphaDonor-specific blood transfusionApoptotic cellsNecrosis factor α expressionRole of CD95LAcute allograft rejectionDonor-specific transfusionGraft-infiltrating cellsHeterotopic cardiac allograftsCytotoxic T cellsTarget cell lysisTNF-alpha expressionTumor necrosis factorExpression of CD95LCD95/CD95LExpression of FasAcute rejectionCardiac allograftsBlood transfusionIntragraft expressionNecrosis factorT cellsCD95 antigenAllografts