Dataset Information

Histone deacetylase inhibition promotes intratumoral CD8⁺ T-cell responses, sensitizing murine breast tumors to anti-PD1.

ABSTRACT: Histone deacetylase (HDAC) inhibitors impair tumor cell proliferation and alter gene expression. However, the impact of these changes on anti-tumor immunity is poorly understood. Here, we showed that the class I HDAC inhibitor, entinostat (ENT), promoted the expression of immune-modulatory molecules, including MHCII, costimulatory ligands, and chemokines on murine breast tumor cells in vitro and in vivo. ENT also impaired tumor growth in vivo-an effect that was dependent on both CD8⁺ T cells and IFN?. Moreover, ENT promoted intratumoral T-cell clonal expansion and enhanced their functional activity. Importantly, ENT sensitized normally unresponsive tumors to the effects of PD1 blockade, predominantly through increases in T-cell proliferation. Our findings suggest that class I HDAC inhibitors impair tumor growth by enhancing the proliferative and functional capacity of CD8⁺ T cells and by sensitizing tumor cells to T-cell recognition.

SUBMITTER: McCaw TR

PROVIDER: S-EPMC6879872 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Histone deacetylase inhibition promotes intratumoral CD8<sup>+</sup> T-cell responses, sensitizing murine breast tumors to anti-PD1.

McCaw Tyler R TR Li Mei M Starenki Dmytro D Liu Mingyong M Cooper Sara J SJ Arend Rebecca C RC Forero Andres A Buchsbaum Donald J DJ Randall Troy D TD

Cancer immunology, immunotherapy : CII 20191112 12

Histone deacetylase (HDAC) inhibitors impair tumor cell proliferation and alter gene expression. However, the impact of these changes on anti-tumor immunity is poorly understood. Here, we showed that the class I HDAC inhibitor, entinostat (ENT), promoted the expression of immune-modulatory molecules, including MHCII, costimulatory ligands, and chemokines on murine breast tumor cells in vitro and in vivo. ENT also impaired tumor growth in vivo-an effect that was dependent on both CD8<sup>+</sup> ...[more]

PMID: 31720815

Similar Datasets

Project description:Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. However, little is known about HDAC expression or function within the optic nerve. As a first step in understanding the role of HDACs in optic nerve, this study examines the spatio-temporal expression patterns of methylated histone 3 (K9), acetylated histone 3 (K18), and HDACs 1-6 and 8-11 in the developing murine optic nerve head.Using RT-qPCR, western blot and immunofluorescence, three stages were analyzed: embryonic day 16 (E16), when astrocyte precursors are found in the optic stalk, postnatal day 5 (P5), when immature astrocytes and oligodendrocytes are found throughout the optic nerve, and P30, when optic nerve astrocytes and oligodendrocytes are mature. Acetylated and methylated histone H3 immunoreactivity was co-localized in the nuclei of most SOX2 positive glia within the optic nerve head and adjacent optic nerve at all developmental stages. HDACs 1-11 were expressed in the optic nerve glial cells at all three stages of optic nerve development in the mouse, but showed temporal differences in overall levels and subcellular localization. HDACs 1 and 2 were predominantly nuclear throughout optic nerve development and glial cell maturation. HDACs 3, 5, 6, 8, and 11 were predominantly cytoplasmic, but showed nuclear localization in at least one stage of optic nerve development. HDACs 4, 9 and10 were predominantly cytoplasmic, with little to no nuclear expression at any time during the developmental stages examined.Our results showing that HDACs 1, 2, 3, 5, 6, 8, and 11 were each localized to the nuclei of SOX2 positive glia at some stages of optic nerve development and maturation and extend previous reports of HDAC expression in the aging optic nerve. These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation and methylation contributes to glial development as well as their injury response.

Dataset Information

Histone deacetylase inhibition promotes intratumoral CD8⁺ T-cell responses, sensitizing murine breast tumors to anti-PD1.

Publications

Histone deacetylase inhibition promotes intratumoral CD8<sup>+</sup> T-cell responses, sensitizing murine breast tumors to anti-PD1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Histone deacetylase inhibition promotes intratumoral CD8+ T-cell responses, sensitizing murine breast tumors to anti-PD1.

Publications

Histone deacetylase inhibition promotes intratumoral CD8<sup>+</sup> T-cell responses, sensitizing murine breast tumors to anti-PD1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Histone deacetylase inhibition promotes intratumoral CD8⁺ T-cell responses, sensitizing murine breast tumors to anti-PD1.