Chronic Myeloid Leukemia: Immunobiology and Novel Immunotherapeutic Approaches
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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.
KeywordsImatinib Chronic Myeloid Leukemia Tyrosine Kinase Inhibitor Dasatinib Nilotinib
Compliance with Ethical Standards
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.
- 8.Pierson BA, Miller JS. CD56+ bright and CD56+ dim natural killer cells in patients with chronic myelogenous leukemia progressively decrease in number, respond less to stimuli that recruit clonogenic natural killer cells, and exhibit decreased proliferation on a per cell basis. Blood. 1996;88(6):2279–87.PubMedGoogle Scholar
- 23.Najjar YG, Finke JH. Clinical perspectives on targeting of myeloid derived suppressor cells in the treatment of cancer. Front Oncol. 2013; 3.Google Scholar