Abstract
Cbx3/HP1γ is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8+ T cells, Cbx3/HP1γ insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8+ T cells, there is an increase of CD8+ effector T cells expressing the stimulatory receptor Klrk1/NKG2D, a decrease in CD4+ CD25+ FOXP3+ regulatory T cells (Treg cells) as well as CD25+ CD4+ T cells expressing the inhibitory receptor CTLA4. Together these changes in the tumor immune environment may have mitigated tumor burden in Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8+ T cells. These findings suggest that targeting Cbx3/HP1γ can represent a rational therapeutic approach to control growth of solid tumors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / transplantation
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CTLA-4 Antigen / metabolism
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Cell Line, Tumor
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Chromosomal Proteins, Non-Histone / deficiency
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Chromosomal Proteins, Non-Histone / genetics*
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Coculture Techniques
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Core Binding Factor Alpha 3 Subunit / metabolism
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Female
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Histones / metabolism
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NK Cell Lectin-Like Receptor Subfamily K / metabolism
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Neoplasms / pathology
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Neoplasms / therapy
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Perforin / genetics
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Perforin / metabolism
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RNA Polymerase II / metabolism
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
Substances
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CTLA-4 Antigen
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Cbx3 protein, mouse
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Chromosomal Proteins, Non-Histone
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Core Binding Factor Alpha 3 Subunit
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Histones
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IFNG protein, mouse
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Klrk1 protein, mouse
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NK Cell Lectin-Like Receptor Subfamily K
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Runx3 protein, mouse
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perforin 1, mouse
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Perforin
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Interferon-gamma
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RNA Polymerase II