Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape

Hsieh, Y.-C., Kirschner, K. and Copland, M. (2021) Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia, 35(5), pp. 1229-1242. (doi: 10.1038/s41375-021-01238-w) (PMID:33833387) (PMCID:PMC8102187)

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Abstract

The quest for treatment-free remission (TFR) and deep molecular response (DMR) in chronic myeloid leukemia (CML) has been profoundly impacted by tyrosine kinase inhibitors (TKIs). Immunologic surveillance of residual leukemic cells is hypothesized to be one of the critical factors in successful TFR, with self-renewing leukemic stem cells implicated in relapse. Immunological characterization in CML may help to develop novel immunotherapies that specifically target residual leukemic cells upon TKI discontinuation to improve TFR rates. This review focuses on immune dysfunction in newly diagnosed CML patients, and the role that TKIs and other therapies have in restoring immune surveillance. Immune dysfunction and immunosurveillance in CML points towards several emerging areas in the key goals of DMR and TFR, including: (1) Aspects of innate immune system, in particular natural killer cells and the newly emerging target plasmacytoid dendritic cells. (2) The adaptive immune system, with promise shown in regard to leukemia-associated antigen vaccine-induced CD8 cytotoxic T-cells (CTL) responses, increased CTL expansion, and immune checkpoint inhibitors. (3) Immune suppressive myeloid-derived suppressor cells and T regulatory cells that are reduced in DMR and TFR. (4) Immunomodulator mesenchymal stromal cells that critically contribute to leukomogenesis through immunosuppressive properties and TKI- resistance. Therapeutic strategies that leverage existing immunological approaches include donor lymphocyte infusions, that continue to be used, often in combination with TKIs, in patients relapsing following allogeneic stem cell transplant. Furthermore, previous standards-of-care, including interferon-α, hold promise in attaining TFR in the post-TKI era. A deeper understanding of the immunological landscape in CML is therefore vital for both the development of novel and the repurposing of older therapies to improve TFR outcomes.

Item Type:Articles
Additional Information:This work was supported by the Professor Tessa Holyoake Memorial Fund (2019; YCH), NHSGGC Endowment Fellowship Funding Award (2021/GN20ON417; YCH) and Leukaemia UK John Goldman fellowship (2019/JGF/003; KK).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kirschner, Dr Kristina and Hsieh, Dr Ya-Ching and Copland, Professor Mhairi
Authors: Hsieh, Y.-C., Kirschner, K., and Copland, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Leukemia
Publisher:Springer Nature
ISSN:0887-6924
ISSN (Online):1476-5551
Published Online:08 April 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Leukemia 35(5): 1229-1242
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306709Early detection of pre-leukaemic clones in the aged haematopoietic compartment using single cell approachesKristina KirschnerLeuka (LEUKA)2019/JGF/003CS - Epigenetics