Long-Term Ibrutinib Therapy Reverses CD8 T Cell Exhaustion in B Cell Chronic Lymphocytic Leukaemia.

Parry, Helen M and Mirajkar, Nikhil and Cutmore, Natasha and Zuo, Jianmin and Long, Heather and Kwok, Marwan and Oldrieve, Ceri and Hudson, Chris and Stankovic, Tatjana and Paneesha, Shankara and Kelly, Melanie and Begum, Jusnara and McSkeane, Tina and Pratt, Guy and Moss, Paul (2019) Long-Term Ibrutinib Therapy Reverses CD8 T Cell Exhaustion in B Cell Chronic Lymphocytic Leukaemia. Frontiers in immunology, 10. p. 2832. ISSN 1664-3224. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.comz795c8c by using their UHB Athens login IDs

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Abstract

Chronic Lymphocytic Leukaemia (CLL) is associated with immune suppression and susceptibility to infection. CD8 T cell numbers are increased and demonstrate elevated expression of PD-1 and impaired function. The mechanisms driving these features of exhaustion are uncertain but are likely to include chronic immune recognition of tumor and/or infectious agents. We investigated the number, phenotype and function of total and virus-specific CD8+ T cells in 65 patients with CLL and 14 patients undergoing long-term ibrutinib therapy (median 21 months). Ibrutinib substantially reduced the number of both CD3+ T cells and CD8+ T cells. Importantly, this was associated with a reduction in PD-1 expression on CD8+ T cells (median 28 vs. 24%; = 0.042) and 3.5 fold increase in cytokine production following mitogen stimulation. The influence of ibrutinib on antigen-specific CD8+ T cell function was assessed by HLA-peptide tetramers and revealed increased IFNγ and TNFα cytokine responses following stimulation with CMV or EBV peptides together with a 55% reduction in the frequency of "inflated" virus-specific CD8+ T cells. These findings reveal that long-term ibrutinib therapy is associated with substantial reversal of T cell exhaustion in B-CLL and is likely to contribute to the reduced infection risk seen in association with this agent.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.comz795c8c by using their UHB Athens login IDs
Subjects: QW Microbiology. Immunology
QZ Pathology. Oncology
Divisions: Clinical Support > Immunology
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Depositing User: Jamie Edgar
Date Deposited: 17 Jan 2020 16:19
Last Modified: 17 Jan 2020 16:19
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2771

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