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

TY - JOUR

T1 - 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies

AU - Gang, A O

AU - Frøsig, T M

AU - Brimnes, M K

AU - Lyngaa, R

AU - Treppendahl, M B

AU - Grønbæk, K

AU - Dufva, I H

AU - Straten, P Thor

AU - Hadrup, S R

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

U2 - 10.1038/bcj.2014.14

DO - 10.1038/bcj.2014.14

M3 - Journal article

C2 - 24681961

SN - 2044-5385

VL - 4

SP - 1

EP - 9

JO - Blood Cancer Journal

JF - Blood Cancer Journal

IS - 3

M1 - e197

ER -