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Full-Text Articles in Allergy and Immunology
The Dna Methyltransferase Inhibitor, Guadecitabine, Targets Tumor-Induced Myelopoiesis And Recovers T Cell Activity To Slow Tumor Growth, Andrea J. Elkovich
The Dna Methyltransferase Inhibitor, Guadecitabine, Targets Tumor-Induced Myelopoiesis And Recovers T Cell Activity To Slow Tumor Growth, Andrea J. Elkovich
Theses and Dissertations
Myeloid Derived Suppressor Cells (MDSC) represent a significant hurdle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous studies have reported on the myelo-depletive effects of certain chemotherapies. Using guadecitabine, a next-generation DNA methyltransferase inhibitor (DNMTi), we observed significantly reduced tumor burden in the 4T1 murine mammary carcinoma model. Guadecitabine treatment prevents excessive tumor-induced myeloid proliferation and systemic accumulation, and skews remaining MDSCs toward a beneficial antigen-presenting phenotype. Together, this alters the splenic environment to improve T cell activation and interferon-gamma (IFNg) production. Additionally, guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor …