title: GPC3 expression in mouse ovarian cancer induces GPC3‑specific T cell-mediated immune response through M1 macrophages and suppresses tumor growth.
abstract: Glypican-3 (GPC3) is specifically expressed in ovarian clear cell carcinoma (OCCC), hepatocellular carci-noma (HCC), and melanoma and lung cancer. GPC3 is being explored as a potential candidate for OCCC and HCC immunotherapy. As a tumor-associated antigen, induction of immune response of GPC3 in ovarian cancer remains elusive. We established a GPC3 transgenic mouse ovarian cancer cell line, OV2944-HM-1 (HM-1), and used the intraperitoneal ovarian cancer mouse model to investigate immune response in GPC3-expressing tumor. We found that GPC3 expression in the tumor increased F4/80+CD86+ macrophage (M1) proportion and caused GPC3-specific CD8+ T cell immune responses, and prolonged mouse survival. Our results demonstrated that GPC3 expression induced T cell-mediated immune response in this mouse ovarian cancer model and also provided supportive evidence that GPC3 is an ideal target for ovarian cancer immunotherapy.
authors.affiliation: Bio-Databases Institute of Reproductive and Developmental Medicine, Nagoya 458-0818, Japan.
authors.forename: Chenhong
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466‑8550, Japan.
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466‑8550, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466‑8550, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.affiliation: Department of Cancer Biology, Nagoya University School of Medicine, Nagoya 466‑8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
authors.affiliation: Bio-Databases Institute of Reproductive and Developmental Medicine, Nagoya 458-0818, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Koya
authors.affiliation: Bell Research Center for Reproductive Health and Cancer, Nagoya 458-0818, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Daimon
authors.affiliation: Bell Research Center for Reproductive Health and Cancer, Nagoya 458-0818, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466‑8550, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D053673:Glypicans / Q000235:genetics* / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000166:cytology
chemical_list: C000602440:GPC3 protein, mouse; D053673:Glypicans