title: 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies.
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.
authors.affiliation: Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Herlev, Denmark.
authors.forename: A O
authors.initials: AO
authors.lastname: Gang
authors.affiliation: 1] Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Herlev, Denmark [2] Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T M
authors.initials: TM
authors.lastname: Frøsig
authors.affiliation: Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Herlev, Denmark.
authors.forename: M K
authors.initials: MK
authors.lastname: Brimnes
authors.affiliation: Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Herlev, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Lyngaa
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: M B
authors.initials: MB
authors.lastname: Treppendahl
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Grønbæk
authors.affiliation: Department of Hematology, University Hospital Herlev, Herlev, Denmark.
authors.forename: I H
authors.initials: IH
authors.lastname: Dufva
authors.affiliation: Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Herlev, Denmark.
authors.forename: P Thor
authors.initials: PT
authors.lastname: Straten
authors.affiliation: Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev, Herlev, Denmark.
authors.forename: S R
authors.initials: SR
authors.lastname: Hadrup