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Chronic Myeloid Leukemia: Immunobiology and Novel Immunotherapeutic Approaches

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Abstract

Imatinib has revolutionized the treatment and prognosis of chronic myeloid leukemia (CML) with survival rates now approaching those of the age-matched healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI) treatment, it is necessary to develop complementary therapies to target minimal residual disease. Recent findings by a number of investigators in both CML mouse models and CML patients offer evidence that many factors in the leukemic microenvironment can collectively contribute to immune escape, including expansion of myeloid-derived suppressor cells, programmed death-1/programmed death-1 ligand interactions resulting in T-cell impairment, expression of soluble suppressive factors such as soluble CD25, and down-regulation of MHC molecules by CML cells. Other investigators have studied the role of cytokines on the resistance to TKIs by leukemic stem cells (LSCs) and have highlighted the implication of the JAK/STAT pathway as well as the interleukin 1 (IL-1) signaling pathway. Distinct immunologic strategies have been considered to harness the immune system or trigger LSC death to allow more CML patients to discontinue TKI treatment (so-called functional cure). Successful immunotherapy and TKI combination and the optimal timing of immunotherapy determination represent major challenges for the future.

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Authors and Affiliations

  1. INSERM CIC 1402, CHU de Poitiers, Poitiers, France

    Emilie Cayssials & Francois Guilhot

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  1. Emilie Cayssials
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  2. Francois Guilhot
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Correspondence to Francois Guilhot.

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This work was supported by grants from Ligue Nationale contre Cancer and Institut National de la Santé et de la Recherche Médicale.

Conflicts of Interest

Emilie Cayssials and Francois Guilhot declare no conflicts of interests.

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Cayssials, E., Guilhot, F. Chronic Myeloid Leukemia: Immunobiology and Novel Immunotherapeutic Approaches. BioDrugs 31, 143–149 (2017). https://doi.org/10.1007/s40259-017-0225-6

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