BJHaem 260919 FIN[33].pdf (2.45 MB)
Increased frequency of CD4+PD-1+HLA-DR+ T cells is associated with disease progression in CLL
journal contribution
posted on 2023-06-10, 04:55 authored by Lauren Elston, Chris Fegan, Robert Hills, Shaikh S Hashimdeen, Elizabeth Walsby, Peter Henley, Christopher PepperChristopher Pepper, Stephen ManChronic lymphocytic leukaemia (CLL) patients often have abnormal expansions of CD4+ and CD8+ T cells and this can be associated with progressive disease. To characterise the key T-cell populations involved in this phenomenon, we used flow cytometry and 11 phenotypic markers to study 74 CLL patients and 14 controls. T cells of CLL patients were more phenotypically complex than those of healthy controls with significant increases in the frequencies of CD4 and CD8 memory T cells expressing exhaustion-, activation- and senescence-associated markers. Multivariate analysis of 111 different T-cell subsets showed that high frequencies of four subsets (three CD8 and one CD4) were associated with shorter progression-free survival. The most significant association was with CD4+HLA-DR+PD-1+ T cells, and patients could be stratified into high- and low-risk groups based on the frequency of these T cells. The expansion of this CD4+ subset could not be accounted for by age, cytomegalovirus infection or increases in Treg cells. Overall, these results highlight two relatively simple biomarkers, percentage CD8+ and percentage CD4+PD-1+HLA-DR+ T cells, which can be used to risk-stratify CLL patients, independent of other tumour-associated markers. They also provide further evidence for the pivotal role of T cells in modulating the pathology of CLL.
History
Publication status
- Published
File Version
- Accepted version
Journal
British Journal of HaematologyISSN
0007-1048Publisher
WileyExternal DOI
Issue
6Volume
188Page range
872-880Event location
EnglandDepartment affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-09-29First Open Access (FOA) Date
2022-10-25First Compliant Deposit (FCD) Date
2022-10-25Usage metrics
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