Abstract
Immunotherapy confers durable clinical benefit to melanoma, lung, and kidney cancer patients. Challengingly, most other solid tumors, including ovarian carcinoma, are not particularly responsive to immunotherapy, so combination with a complementary therapy may be beneficial. Recent findings suggest that epigenetic modifying drugs can prime antitumor immunity by increasing expression of tumor-associated antigens, chemokines, and activating ligands by cancer cells as well as cytokines by immune cells. This review, drawing from both preclinical and clinical data, describes some of the mechanisms of action that enable DNA methyltransferase inhibitors to facilitate the establishment of antitumor immunity.
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Abbreviations
- AML:
-
Acute myeloid leukemia
- AZA:
-
Azacitidine
- CLL:
-
Chronic lymphocytic leukemia
- CTA:
-
Cancer testis antigen
- CTL:
-
Cytotoxic T lymphocyte
- DAC:
-
Decitabine
- DNMT:
-
DNA methyltransferases
- DNMTi:
-
DNA methyltransferase inhibitor
- HDAC:
-
Histone deacetylase
- MAGE:
-
Melanoma-associated antigen
- MDS:
-
Myelodysplastic syndrome
- MDSC:
-
Myeloid-derived suppressor cell
- MHC I:
-
Major histocompatibility complex class I
- NK cells:
-
Natural killer cells
- NKG2D:
-
Natural-killer group 2, member D
- NSCLC:
-
Non-small cell lung cancer
- KIR:
-
Killer immunoglobulin-like receptor
- Tregs:
-
Regulatory T cells
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Acknowledgments
We thank the Ovarian Cancer Research Fund (Liz Tilberis Scholar award) and the Susan F. Smith Center for Women’s Cancer for supporting this work.
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This paper is a Focussed Research Review based on a presentation given at the Fourth International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2015), held in Ljubljana, Slovenia, 27th–30th April 2015. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.
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Saleh, M.H., Wang, L. & Goldberg, M.S. Improving cancer immunotherapy with DNA methyltransferase inhibitors. Cancer Immunol Immunother 65, 787–796 (2016). https://doi.org/10.1007/s00262-015-1776-3
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DOI: https://doi.org/10.1007/s00262-015-1776-3