Control of chronic lymphocytic leukemia development by clonally-expanded CD8 + T-cells that undergo functional exhaustion in secondary lymphoid tissues

• Verfasst von: Hanna, Bola S. [VerfasserIn]
• Verfasst von: Schmidt, Manfred [VerfasserIn]
• Verfasst von: Gabriel, Richard [VerfasserIn]
• Verfasst von: Lichter, Peter [VerfasserIn]
• Verfasst von: Seiffert, Martina [VerfasserIn]
• Titel: Control of chronic lymphocytic leukemia development by clonally-expanded CD8 + T-cells that undergo functional exhaustion in secondary lymphoid tissues
• Verf.angabe: 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
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 13 S.
• Fussnoten: Published: 28 September 2018 ; Gesehen am 05.07.2019
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2019
• Band/Heft Quelle: 33(2019), 3, Seite 625-637
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/s41375-018-0250-6
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1668685779

Abstract

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.