Featured Publications
Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors
Xu S, Chaudhary O, Rodríguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AFM, Williams A, Schulze I, Farsakoglu Y, Varanasi SK, Low JS, Tang W, Wang H, McDonald B, Tripple V, Downes M, Evans RM, Abumrad NA, Merghoub T, Wolchok JD, Shokhirev MN, Ho PC, Witztum JL, Emu B, Cui G, Kaech SM. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors. Immunity 2021, 54: 1561-1577.e7. PMID: 34102100, PMCID: PMC9273026, DOI: 10.1016/j.immuni.2021.05.003.Peer-Reviewed Original ResearchConceptsTumor microenvironmentCell dysfunctionLipid peroxidationLipid accumulationOxidized low-density lipoproteinExpression of CD36Low-density lipoproteinCommon metabolic alterationsScavenger receptor CD36Intratumoral CD8Immune dysfunctionEffector TGlutathione peroxidase 4CD8Effector functionsInhibition of p38Metabolic alterationsReceptor CD36Therapeutic avenuesScavenger receptorsDysfunctionWT counterpartsTILsCell functionCD36The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell function
2021
NASH limits anti-tumour surveillance in immunotherapy-treated HCC
Pfister D, Núñez NG, Pinyol R, Govaere O, Pinter M, Szydlowska M, Gupta R, Qiu M, Deczkowska A, Weiner A, Müller F, Sinha A, Friebel E, Engleitner T, Lenggenhager D, Moncsek A, Heide D, Stirm K, Kosla J, Kotsiliti E, Leone V, Dudek M, Yousuf S, Inverso D, Singh I, Teijeiro A, Castet F, Montironi C, Haber PK, Tiniakos D, Bedossa P, Cockell S, Younes R, Vacca M, Marra F, Schattenberg JM, Allison M, Bugianesi E, Ratziu V, Pressiani T, D’Alessio A, Personeni N, Rimassa L, Daly AK, Scheiner B, Pomej K, Kirstein MM, Vogel A, Peck-Radosavljevic M, Hucke F, Finkelmeier F, Waidmann O, Trojan J, Schulze K, Wege H, Koch S, Weinmann A, Bueter M, Rössler F, Siebenhüner A, De Dosso S, Mallm JP, Umansky V, Jugold M, Luedde T, Schietinger A, Schirmacher P, Emu B, Augustin HG, Billeter A, Müller-Stich B, Kikuchi H, Duda DG, Kütting F, Waldschmidt DT, Ebert MP, Rahbari N, Mei HE, Schulz AR, Ringelhan M, Malek N, Spahn S, Bitzer M, Ruiz de Galarreta M, Lujambio A, Dufour JF, Marron TU, Kaseb A, Kudo M, Huang YH, Djouder N, Wolter K, Zender L, Marche PN, Decaens T, Pinato DJ, Rad R, Mertens JC, Weber A, Unger K, Meissner F, Roth S, Jilkova ZM, Claassen M, Anstee QM, Amit I, Knolle P, Becher B, Llovet JM, Heikenwalder M. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 2021, 592: 450-456. PMID: 33762733, PMCID: PMC8046670, DOI: 10.1038/s41586-021-03362-0.Peer-Reviewed Original ResearchConceptsNon-alcoholic steatohepatitisNon-viral hepatocellular carcinomaAnti-PD1 treatmentT cellsHepatocellular carcinomaNASH-HCCImmune surveillanceRandomized phase III clinical trialsPhase III clinical trialsAberrant T cell activationAnti-PDL1 treatmentAnti-tumor surveillanceStudy of immunotherapyDepletion of CD8Advanced hepatocellular carcinomaTumor immune surveillanceStratification of patientsBiomarker-based stratificationT cell activationAdjuvant treatmentOverall survivalTNF neutralizationDeath-1Immune therapyTherapeutic immunotherapy
2018
HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers
Farhadian S, Jalbert E, Deng Y, Goetz MB, Park LS, Justice A, Dubrow R, Emu B. HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2018, 77: 337-344. PMID: 29140874, PMCID: PMC5807137, DOI: 10.1097/qai.0000000000001595.Peer-Reviewed Original ResearchConceptsCD8 T cellsT-cell markersCD4 T cellsHIV infectionT cellsAntiretroviral therapyEffector memory CD4 T cellsImmune systemVeterans Aging Cohort StudyMemory CD4 T cellsNaive CD4 T cellsAging Cohort StudyT cell subsetsT-cell phenotypeCopies/mLCross-sectional studyRace/ethnicityChronic HIVUninfected subjectsUninfected menCohort studyHIV diseaseHigher proportionHIV serostatusHIV status
2014
Composition and Function of T Cell Subpopulations Are Slow to Change Despite Effective Antiretroviral Treatment of HIV Disease
Emu B, Moretto WJ, Hoh R, Krone M, Martin JN, Nixon DF, Deeks SG, McCune JM. Composition and Function of T Cell Subpopulations Are Slow to Change Despite Effective Antiretroviral Treatment of HIV Disease. PLOS ONE 2014, 9: e85613. PMID: 24465619, PMCID: PMC3897457, DOI: 10.1371/journal.pone.0085613.Peer-Reviewed Original ResearchConceptsT cell subpopulationsT cellsCell subpopulationsViral loadCMV-specific T-cell responsesNaïve T cell numbersLong-term viral suppressionIncrease of CD4Effective antiretroviral treatmentT cell frequenciesUndetectable viral loadT cell numbersT-cell depletionT cell responsesT-cell phenotypeNormal immune systemT cell populationsLow Ki67 expressionT cell functionIndependent homeostatic regulationDifferent proliferative responsesAntiretroviral therapyViral suppressionHIV diseaseAntiretroviral treatment
2011
HIV disease progression correlates with the generation of dysfunctional naive CD8low T cells
Favre D, Stoddart CA, Emu B, Hoh R, Martin JN, Hecht FM, Deeks SG, McCune JM. HIV disease progression correlates with the generation of dysfunctional naive CD8low T cells. Blood 2011, 117: 2189-2199. PMID: 21200021, PMCID: PMC3062328, DOI: 10.1182/blood-2010-06-288035.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCalcium SignalingCD8-Positive T-LymphocytesDisease ProgressionHIV InfectionsHumansIn Vitro TechniquesInterferon alpha-2Interferon-alphaInterleukin-2Major Histocompatibility ComplexMART-1 AntigenMiceMice, SCIDMice, TransgenicMiddle AgedP38 Mitogen-Activated Protein KinasesPhosphorylationReceptors, Antigen, T-CellRecombinant ProteinsSignal TransductionThymus GlandUp-RegulationViral LoadConceptsPeripheral blood mononuclear cellsT cellsHIV diseaseHIV infectionSCID-hu Thy/Liv mouse modelMajor histocompatibility complex class ICD8low T cellsProgressive HIV diseaseHIV disease progressionHistocompatibility complex class IBlood mononuclear cellsInterferon-α treatmentAntigen-presenting cellsComplex class IT cell receptor complexCD8β chainNaive compartmentΑ treatmentMononuclear cellsDisease progressionMouse modelStromal cellsLow expressionClass IMHC
2008
HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control
Emu B, Sinclair E, Hatano H, Ferre A, Shacklett B, Martin JN, McCune JM, Deeks SG. HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control. Journal Of Virology 2008, 82: 5398-5407. PMID: 18353945, PMCID: PMC2395228, DOI: 10.1128/jvi.02176-07.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesHealthHistocompatibility Antigens Class IHIV InfectionsHIV-1HumansInterferon-gammaInterleukin-2Time FactorsConceptsT cell responsesHLA class IElite controllersT cellsViremic controllersVirus controlClass IInterleukin-2HIV-specific T-cell responsesT cell-mediated controlUndetectable HIV RNA levelsHuman immunodeficiency virus (HIV) infectionHLA class I allelesProtective class IHIV RNA levelsHLA class I polymorphismImmunodeficiency virus infectionLong-term virus controlCell-mediated controlHuman immunodeficiency virusClass I allelesClass I polymorphismAntiretroviral therapyHIV controllersHIV transmission
2005
Phenotypic, Functional, and Kinetic Parameters Associated with Apparent T-Cell Control of Human Immunodeficiency Virus Replication in Individuals with and without Antiretroviral Treatment
Emu B, Sinclair E, Favre D, Moretto WJ, Hsue P, Hoh R, Martin JN, Nixon DF, McCune JM, Deeks SG. Phenotypic, Functional, and Kinetic Parameters Associated with Apparent T-Cell Control of Human Immunodeficiency Virus Replication in Individuals with and without Antiretroviral Treatment. Journal Of Virology 2005, 79: 14169-14178. PMID: 16254352, PMCID: PMC1280210, DOI: 10.1128/jvi.79.22.14169-14178.2005.Peer-Reviewed Original ResearchConceptsHIV-specific T cellsT cellsT cell activationHIV diseaseImmune activationHuman immunodeficiency virus (HIV) replicationAdvanced HIV diseaseDrug-resistant viremiaGeneralized immune activationHIV-specific ILMultidrug-resistant HIVQuiescent immune systemActive antiretroviral therapyCytokine flow cytometryT cell controlHigh-level viremiaLow-level viremiaPresence of HIVT cell subsetsHuman immunodeficiency virusImmunodeficiency virus replicationT cell subpopulationsAbsence of therapyPresence of therapyAntiretroviral therapy