CD8+ T-cells of CLL-bearing mice acquire a transcriptional program of T-cell activation and exhaustion.
Leuk Lymphoma
; 61(2): 351-356, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31519123
ABSTRACT
Chronic lymphocytic leukemia (CLL) is associated with an accumulation of oligoclonal CD8+ effector T-cells, which control leukemia progression in mice, but gradually acquire a dysfunctional phenotype along with disease progression. Exhaustion of CD8+ T-cells is characterized by increased expression of inhibitory receptors like PD-1, decreased proliferation, and reduced effector function such as cytokine production, which reduces anti-tumor control. Despite the accumulation of exhausted PD-1+ CD8+ T-cells in secondary lymphoid organs of CLL patients, immune checkpoint blockade as a means to reinvigorate anti-tumor T-cell activity has not shown the expected efficacy. This highlights the need for a better understanding of T-cell exhaustion in CLL. Here, we uncover the transcriptional program of T-cell exhaustion in CLL by comparing naïve with dysfunctional effector CD8+ T-cells with high PD-1 expression from mice after adoptive transfer of Eµ-TCL1 leukemic cells. Our data provide clear evidence for activation-induced dysfunction of CD8+ T-cells in the CLL microenvironment and assess the heterogeneity in the expression of functionally relevant proteins in specific clusters of CD8+ T-cells at a single-cell level.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Linfocítica Crónica de Células B
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania