Luo Chenhong, Shibata Kiyosumi, Suzuki Shiro, Kajiyama Hiroaki, Senga Takeshi, Koya Yoshihiro, Daimon Mina, Yamashita Mamoru, Kikkawa Fumitaka
Bio-Databases Institute of Reproductive and Developmental Medicine, Nagoya 458-0818, Japan.
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466‑8550, Japan.
Oncol Rep. 2014 Sep;32(3):913-21. doi: 10.3892/or.2014.3300. Epub 2014 Jul 2.
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.
磷脂酰肌醇蛋白聚糖-3(GPC3)在卵巢透明细胞癌(OCCC)、肝细胞癌(HCC)、黑色素瘤和肺癌中特异性表达。GPC3正作为OCCC和HCC免疫治疗的潜在候选物进行研究。作为一种肿瘤相关抗原,GPC3在卵巢癌中诱导免疫反应的机制仍不清楚。我们建立了一种GPC3转基因小鼠卵巢癌细胞系OV2944-HM-1(HM-1),并使用腹腔内卵巢癌小鼠模型来研究表达GPC3的肿瘤中的免疫反应。我们发现肿瘤中GPC3的表达增加了F4/80+CD86+巨噬细胞(M1)的比例,并引发了GPC3特异性CD8+T细胞免疫反应,延长了小鼠的生存期。我们的结果表明,在该小鼠卵巢癌模型中,GPC3的表达诱导了T细胞介导的免疫反应,也为GPC3是卵巢癌免疫治疗的理想靶点提供了支持性证据。