Open AccessSelective targeting of different populations of myeloid-derived suppressor cells by histone deacetylase inhibitors
Author(s) -
Ayumi Hashimoto,
Takeshi Fukumoto,
Rugang Zhang,
Dmitry I. Gabrilovich
Publication year - 2020
Publication title -
cancer immunology, immunotherapy/cancer immunology and immunotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.389
H-Index - 115
eISSN - 1432-0851
pISSN - 0340-7004
DOI - 10.1007/s00262-020-02588-7
Subject(s) - hdac6 , histone deacetylase , cancer research , immune system , myeloid derived suppressor cell , suppressor , chemistry , hdac1 , tumor progression , myeloid , cancer , immunology , pharmacology , histone , biology , medicine , biochemistry , gene
Myeloid-derived suppressor cells (MDSCs) are widely implicated in negative regulation of immune responses in cancer. Inhibition of class I histone deacetylases (HDAC) with entinostat has anti-MDSC activity. However, as single agent, it did not delay tumor growth in EL4 and LLC tumor models. Here, we found that entinostat reduced immune suppressive activity of only one type of MDSC-polymorphonuclear, PMN-MDSC, whereas it had no effect on monocytic M-MDSC or macrophages. M-MDSC had high amount of class II HDAC-HDAC6, which was further increased after the treatment of mice with entinostat. Inhibition of HDAC6 with ricolinostat reduced suppressive activity of M-MDSC, but did not affect PMN-MDSC or delayed tumor growth. However, combination of entinostat and ricolinostat abrogated suppressive activity of both populations of MDSC and substantially delayed tumor progression. Thus, inactivation of MDSC required targeting of both major subsets of these cells via inhibitors of class I and class II HDAC.