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| Home > In process > Mechanisms 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. > print |
| Home > In process > Mechanisms 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. > print |
| 001 | 258656 | ||
| 005 | 20230620112130.0 | ||
| 024 | 7 | _ | |a 10.1182/blood-2015-02-626754 |2 doi |
| 024 | 7 | _ | |a pmid:25979947 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC4497962 |2 pmc |
| 024 | 7 | _ | |a 0006-4971 |2 ISSN |
| 024 | 7 | _ | |a 1528-0020 |2 ISSN |
| 037 | _ | _ | |a DZNE-2023-00629 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a McClanahan, Fabienne |0 0000-0001-5521-3271 |b 0 |
| 245 | _ | _ | |a Mechanisms 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. |
| 260 | _ | _ | |a Washington, DC |c 2015 |b American Society of Hematology |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1687252840_3102 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a T-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. |
| 536 | _ | _ | |a 899 - ohne Topic (POF4-899) |0 G:(DE-HGF)POF4-899 |c POF4-899 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a B7-H1 Antigen |2 NLM Chemicals |
| 650 | _ | 7 | |a Cd274 protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Immunoglobulin mu-Chains |2 NLM Chemicals |
| 650 | _ | 7 | |a Pdcd1 protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Programmed Cell Death 1 Receptor |2 NLM Chemicals |
| 650 | _ | 7 | |a Proto-Oncogene Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Tcl1 protein, mouse |2 NLM Chemicals |
| 650 | _ | 2 | |a Aging: genetics |2 MeSH |
| 650 | _ | 2 | |a Aging: immunology |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a B7-H1 Antigen: physiology |2 MeSH |
| 650 | _ | 2 | |a CD8-Positive T-Lymphocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a Cell Differentiation: genetics |2 MeSH |
| 650 | _ | 2 | |a Cell Differentiation: immunology |2 MeSH |
| 650 | _ | 2 | |a Cells, Cultured |2 MeSH |
| 650 | _ | 2 | |a Disease Models, Animal |2 MeSH |
| 650 | _ | 2 | |a Immunoglobulin mu-Chains: genetics |2 MeSH |
| 650 | _ | 2 | |a Leukemia, Lymphocytic, Chronic, B-Cell: genetics |2 MeSH |
| 650 | _ | 2 | |a Leukemia, Lymphocytic, Chronic, B-Cell: immunology |2 MeSH |
| 650 | _ | 2 | |a Leukemia, Lymphocytic, Chronic, B-Cell: pathology |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Mice, Transgenic |2 MeSH |
| 650 | _ | 2 | |a Programmed Cell Death 1 Receptor: physiology |2 MeSH |
| 650 | _ | 2 | |a Proto-Oncogene Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Signal Transduction: immunology |2 MeSH |
| 700 | 1 | _ | |a Riches, John C |b 1 |
| 700 | 1 | _ | |a Miller, Shaun |b 2 |
| 700 | 1 | _ | |a Day, William P |b 3 |
| 700 | 1 | _ | |a Kotsiou, Eleni |b 4 |
| 700 | 1 | _ | |a Neuberg, Donna |0 0000-0003-2566-3145 |b 5 |
| 700 | 1 | _ | |a Croce, Carlo M |0 0000-0003-3788-1457 |b 6 |
| 700 | 1 | _ | |a Capasso, Melania |0 P:(DE-2719)2811780 |b 7 |u dzne |
| 700 | 1 | _ | |a Gribben, John G |0 0000-0002-8505-7430 |b 8 |
| 773 | _ | _ | |a 10.1182/blood-2015-02-626754 |g Vol. 126, no. 2, p. 212 - 221 |0 PERI:(DE-600)1468538-3 |n 2 |p 212 - 221 |t Blood |v 126 |y 2015 |x 0006-4971 |
| 856 | 4 | _ | |u https://ashpublications.org/blood/article/126/2/212/34507/Mechanisms-of-PD-L1-PD-1-mediated-CD8-T-cell |
| 910 | 1 | _ | |a External Institute |0 I:(DE-HGF)0 |k Extern |b 7 |6 P:(DE-2719)2811780 |
| 913 | 1 | _ | |a DE-HGF |b Programmungebundene Forschung |l ohne Programm |1 G:(DE-HGF)POF4-890 |0 G:(DE-HGF)POF4-899 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-800 |4 G:(DE-HGF)POF |v ohne Topic |x 0 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a EDITORS |
| 980 | _ | _ | |a I:(DE-2719)1013033 |
| 980 | 1 | _ | |a EXTERN4VITA |
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