5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies.

A.O. Gang, Thomas Mørch Frøsig, M. K. Brimnes, Rikke Birgitte Lyngaa, M. B. Treppendahl, K. Grønbæk, I.H. Dufva, P. Thor Straten, Sine Reker Hadrup

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Abstract

Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival for patients with myelodysplastic syndrome, and the demethylation induces upregulation of cancer-testis antigens. Cancer-testis antigens are well-known targets for immune recognition in cancer, and the immune system may have a role in this treatment regimen. We show here that 5-Azacytidine treatment leads to increased T-cell recognition of tumor cells. T-cell responses against a large panel of cancer-testis antigens were detected before treatment, and these responses were further induced upon initiation of treatment. These characteristics point to an ideal combination of 5-Azacytidine and immune therapy to preferentially boost T-cell responses against cancer-testis antigens. To initiate such combination therapy, essential knowledge is required about the general immune modulatory effect of 5-Azacytidine. We therefore examined potential treatment effects on both immune stimulatory (CD8 and CD4 T cells and Natural Killer (NK) cells) and immune inhibitory cell subsets (myeloid-derived suppressor cells and regulatory T cells). We observed a minor decrease and modulation of NK cells, but for all other populations no effects could be detected. Together, these data support a strategy for combining 5-Azacytidine treatment with immune therapy for potential clinical benefit.
Original languageEnglish
Article numbere197
JournalBlood Cancer Journal
Issue number4
Number of pages9
ISSN2044-5385
DOIs
Publication statusPublished - 2014
Externally publishedYes

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This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

Cite this

Gang, A. O., Frøsig, T. M., Brimnes, M. K., Lyngaa, R. B., Treppendahl, M. B., Grønbæk, K., Dufva, I. H., Straten, P. T., & Hadrup, S. R. (2014). 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies. Blood Cancer Journal, (4), [e197]. https://doi.org/doi:10.1038/bcj.2014.14