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

• Published in: Blood cancer journal (New York) 2014-03, Vol.4 (3), p.e197-e197
• Main Authors: Gang, A O, Frøsig, T M, Brimnes, M K, Lyngaa, R, Treppendahl, M B, Grønbæk, K, Dufva, I H, Straten, P thor, Hadrup, S R
• Format: Article
• Language: English
• Subjects: 692/699/67/1059/2325; 692/699/67/1059/99; 692/699/67/1990/1673; Biomedical and Life Sciences; Biomedicine; Cancer Research; Hematology; Oncology; Original; original-article
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/bcj.2014.14

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.