Control of chronic lymphocytic leukemia development by clonally-expanded CD8 + T-cells that undergo functional exhaustion in secondary lymphoid tissues
Chronic lymphocytic leukemia (CLL) is associated with substantial alterations in T-cell composition and function. However, the role of T-cells in CLL remains largely controversial. Here, we utilized the Eµ-TCL1 mouse model of CLL as well as blood and lymph node samples of CLL patients to investigate...
Gespeichert in:
| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2019
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| In: |
Leukemia
Year: 2018, Jahrgang: 33, Heft: 3, Pages: 625-637 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-018-0250-6 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1038/s41375-018-0250-6 Verlag, Volltext: https://www.nature.com/articles/s41375-018-0250-6 
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| Verfasserangaben: | Bola S. Hanna, Philipp M. Roessner, Haniyeh Yazdanparast, Dolors Colomer, Elias Campo, Sabrina Kugler, Deyan Yosifov, Stephan Stilgenbauer, Manfred Schmidt, Richard Gabriel, Peter Lichter, Martina Seiffert |
| Zusammenfassung: | Chronic lymphocytic leukemia (CLL) is associated with substantial alterations in T-cell composition and function. However, the role of T-cells in CLL remains largely controversial. Here, we utilized the Eµ-TCL1 mouse model of CLL as well as blood and lymph node samples of CLL patients to investigate the existence of anti-tumoral immune responses in CLL, and to characterize involved immune cell populations. Thereby, we identified an oligoclonal CD8+ effector T-cell population that expands along with CLL progression and controls disease development. We further show that a higher percentage of CD8+ effector T-cells produces IFNγ, and demonstrate that neutralization of IFNγ results in faster CLL progression in mice. Phenotypical and functional analyses of expanded CD8+ effector T-cells show significant differences in disease-affected tissues in mice, with cells in secondary lymphoid organs harboring hallmarks of activation-induced T-cell exhaustion. Notably, we further describe a respective population of exhausted CD8+ T-cells that specifically accumulate in lymph nodes, but not in peripheral blood of CLL patients. Collectively, these data emphasize the non-redundant role of CD8+ T-cells in suppressing CLL progression and highlight their dysfunction that can be exploited as target of immunotherapy in this malignancy. |
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| Beschreibung: | Published: 28 September 2018 Gesehen am 05.07.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-018-0250-6 |