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CD8 + T-cells of CLL-bearing mice acquire a transcriptional program of T-cell activation and exhaustion.
- Source :
-
Leukemia & lymphoma [Leuk Lymphoma] 2020 Feb; Vol. 61 (2), pp. 351-356. Date of Electronic Publication: 2019 Sep 13. - Publication Year :
- 2020
-
Abstract
- Chronic lymphocytic leukemia (CLL) is associated with an accumulation of oligoclonal CD8 <superscript>+</superscript> effector T-cells, which control leukemia progression in mice, but gradually acquire a dysfunctional phenotype along with disease progression. Exhaustion of CD8 <superscript>+</superscript> 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 <superscript>+</superscript> CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> T-cells in the CLL microenvironment and assess the heterogeneity in the expression of functionally relevant proteins in specific clusters of CD8 <superscript>+</superscript> T-cells at a single-cell level.
Details
- Language :
- English
- ISSN :
- 1029-2403
- Volume :
- 61
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Leukemia & lymphoma
- Publication Type :
- Academic Journal
- Accession number :
- 31519123
- Full Text :
- https://doi.org/10.1080/10428194.2019.1660972