GPC3 expression in mouse ovarian cancer induces GPC3‑specific T cell-mediated immune response through M1 macrophages and suppresses tumor growth

小鼠卵巢癌中的 GPC3 表达通过 M1 巨噬细胞诱导 GPC3 特异性 T 细胞介导的免疫反应并抑制肿瘤生长

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作者:Chenhong Luo, Kiyosumi Shibata, Shiro Suzuki, Hiroaki Kajiyama, Takeshi Senga, Yoshihiro Koya, Mina Daimon, Mamoru Yamashita, Fumitaka Kikkawa

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.

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