2022
CD137 (4-1BB)-Based Cancer Immunotherapy on Its 25th Anniversary.
Melero I, Sanmamed M, Glez-Vaz J, Luri-Rey C, Wang J, Chen L. CD137 (4-1BB)-Based Cancer Immunotherapy on Its 25th Anniversary. Cancer Discovery 2022, 13: 552-569. PMID: 36576322, DOI: 10.1158/2159-8290.cd-22-1029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnniversaries and Special EventsCD8-Positive T-LymphocytesImmunotherapyMiceNeoplasmsSignal TransductionTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAnti-CD137 monoclonal antibodiesT cell antitumor immunitySevere liver inflammationTolerable safety profileCancer immunotherapy strategiesNatural killer lymphocytesSingle-agent activityNon-Hodgkin lymphomaEarly phase trialsChimeric antigen receptorCD137 agonistsEnhanced CD8Unacceptable toxicityAntitumor immunityLiver inflammationImmunotherapy strategiesSafety profileCancer immunotherapyKiller lymphocytesClinical activityAgonist antibodyPharmacodynamic activityMouse modelCD137Costimulatory receptorsThe CD8α–PILRα interaction maintains CD8+ T cell quiescence
Zheng L, Han X, Yao S, Zhu Y, Klement J, Wu S, Ji L, Zhu G, Cheng X, Tobiasova Z, Yu W, Huang B, Vesely MD, Wang J, Zhang J, Quinlan E, Chen L. The CD8α–PILRα interaction maintains CD8+ T cell quiescence. Science 2022, 376: 996-1001. PMID: 35617401, DOI: 10.1126/science.aaz8658.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensCD8 AntigensCD8-Positive T-LymphocytesDendritic CellsGene DeletionLymphocyte ActivationMembrane GlycoproteinsMiceReceptors, ImmunologicConceptsT cell quiescenceT cellsT cell pool sizeMaintenance of CD8Peripheral lymphoid organsCell quiescenceMemory CD8Antigen exposureLymphoid organsActivation phenotypeCD8Specific antigenCD8αInducible deletionCell pool sizeDiverse antigensAntigenMolecular mechanismsBroad repertoireExposureCellsQuiescent stateTumorsMicePILRα
2021
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesFemaleHumansImmunotherapyLung NeoplasmsMaleMiceMice, Inbred NODProspective StudiesTumor MicroenvironmentConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer