Histone deacetylase (HDAC) inhibitor ACY241 enhances anti-tumor activities of antigen-specific central memory cytotoxic T lymphocytes against multiple myeloma and solid tumors.

ABSTRACT: Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138⁺ MM cells, CD4⁺CD25⁺FoxP3⁺ regulatory T cells, and HLA-DR^Low/-CD11b⁺CD33⁺ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8⁺ T cells and of immune checkpoints in bone marrow cells from myeloma patients. ACY241 increased B7 (CD80, CD86) and MHC (Class I, Class II) expression on tumor and dendritic cells. We further evaluated the effect of ACY241 on antigen-specific cytotoxic T lymphocytes

SUBMITTER: Bae J 

PROVIDER: S-EPMC6537609 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature