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000258656 0247_ $$2doi$$a10.1182/blood-2015-02-626754
000258656 0247_ $$2pmid$$apmid:25979947
000258656 0247_ $$2pmc$$apmc:PMC4497962
000258656 0247_ $$2ISSN$$a0006-4971
000258656 0247_ $$2ISSN$$a1528-0020
000258656 037__ $$aDZNE-2023-00629
000258656 041__ $$aEnglish
000258656 082__ $$a610
000258656 1001_ $$00000-0001-5521-3271$$aMcClanahan, Fabienne$$b0
000258656 245__ $$aMechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.
000258656 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2015
000258656 3367_ $$2DRIVER$$aarticle
000258656 3367_ $$2DataCite$$aOutput Types/Journal article
000258656 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1687252840_3102
000258656 3367_ $$2BibTeX$$aARTICLE
000258656 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000258656 3367_ $$00$$2EndNote$$aJournal Article
000258656 520__ $$aT-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity.
000258656 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0
000258656 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000258656 650_7 $$2NLM Chemicals$$aB7-H1 Antigen
000258656 650_7 $$2NLM Chemicals$$aCd274 protein, mouse
000258656 650_7 $$2NLM Chemicals$$aImmunoglobulin mu-Chains
000258656 650_7 $$2NLM Chemicals$$aPdcd1 protein, mouse
000258656 650_7 $$2NLM Chemicals$$aProgrammed Cell Death 1 Receptor
000258656 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins
000258656 650_7 $$2NLM Chemicals$$aTcl1 protein, mouse
000258656 650_2 $$2MeSH$$aAging: genetics
000258656 650_2 $$2MeSH$$aAging: immunology
000258656 650_2 $$2MeSH$$aAnimals
000258656 650_2 $$2MeSH$$aB7-H1 Antigen: physiology
000258656 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000258656 650_2 $$2MeSH$$aCell Differentiation: genetics
000258656 650_2 $$2MeSH$$aCell Differentiation: immunology
000258656 650_2 $$2MeSH$$aCells, Cultured
000258656 650_2 $$2MeSH$$aDisease Models, Animal
000258656 650_2 $$2MeSH$$aImmunoglobulin mu-Chains: genetics
000258656 650_2 $$2MeSH$$aLeukemia, Lymphocytic, Chronic, B-Cell: genetics
000258656 650_2 $$2MeSH$$aLeukemia, Lymphocytic, Chronic, B-Cell: immunology
000258656 650_2 $$2MeSH$$aLeukemia, Lymphocytic, Chronic, B-Cell: pathology
000258656 650_2 $$2MeSH$$aMice
000258656 650_2 $$2MeSH$$aMice, Transgenic
000258656 650_2 $$2MeSH$$aProgrammed Cell Death 1 Receptor: physiology
000258656 650_2 $$2MeSH$$aProto-Oncogene Proteins: genetics
000258656 650_2 $$2MeSH$$aSignal Transduction: immunology
000258656 7001_ $$aRiches, John C$$b1
000258656 7001_ $$aMiller, Shaun$$b2
000258656 7001_ $$aDay, William P$$b3
000258656 7001_ $$aKotsiou, Eleni$$b4
000258656 7001_ $$00000-0003-2566-3145$$aNeuberg, Donna$$b5
000258656 7001_ $$00000-0003-3788-1457$$aCroce, Carlo M$$b6
000258656 7001_ $$0P:(DE-2719)2811780$$aCapasso, Melania$$b7$$udzne
000258656 7001_ $$00000-0002-8505-7430$$aGribben, John G$$b8
000258656 773__ $$0PERI:(DE-600)1468538-3$$a10.1182/blood-2015-02-626754$$gVol. 126, no. 2, p. 212 - 221$$n2$$p212 - 221$$tBlood$$v126$$x0006-4971$$y2015
000258656 8564_ $$uhttps://ashpublications.org/blood/article/126/2/212/34507/Mechanisms-of-PD-L1-PD-1-mediated-CD8-T-cell
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000258656 980__ $$ajournal
000258656 980__ $$aEDITORS
000258656 980__ $$aI:(DE-2719)1013033
000258656 9801_ $$aEXTERN4VITA