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

AO Gang, TM Frøsig, MK Brimnes, R Lyngaa… - Blood cancer …, 2014 - nature.com
AO Gang, TM Frøsig, MK Brimnes, R Lyngaa, MB Treppendahl, K Grønbæk, IH Dufva…
Blood cancer journal, 2014nature.com
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 …
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.
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