title: Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+T cells.
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.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Pathology, Boston, MA 02215, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sun
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Pathology, Boston, MA 02215, USA.|Department of Neurobiology and Anatomy, Drexel University, College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
authors.forename: Ngoc
authors.initials: N
authors.lastname: Ha
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Pathology, Boston, MA 02215, USA.|Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Duc-Hung
authors.initials: DH
authors.lastname: Pham
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Frederick
authors.affiliation: Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02215, USA.
authors.forename: Bandana
authors.initials: B
authors.lastname: Sharma
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Naruse
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pipkin
authors.affiliation: Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02215, USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rani E
authors.initials: RE
authors.lastname: George
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Pathology, Boston, MA 02215, USA.
authors.forename: To-Ha
authors.initials: TH
authors.lastname: Thai
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D060908:CTLA-4 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics*; D018920:Coculture Techniques; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism; D005260:Female; D006657:Histones / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; C453799:Cbx3 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D050677:Core Binding Factor Alpha 3 Subunit; D006657:Histones; C000611649:IFNG protein, mouse; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; C493730:Runx3 protein, mouse; C510467:perforin 1, mouse; D054353:Perforin; D007371:Interferon-gamma; D012319:RNA Polymerase II