Journal
EXPERT REVIEW OF HEMATOLOGY
Volume 10, Issue 8, Pages 745-752Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17474086.2017.1346470
Keywords
Acute myeloid leukemia; azacitidine; decitabine; hypomethylating agents; immune effects; myelodysplastic syndrome; NK cells; T-cells
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Funding
- Intramural Research Programs of the National Heart, Lung, and Blood Institute of the National Institutes of Health
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Introduction: Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.
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