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

Oncol Rep. 2014 Sep;32(3):913-21. doi: 10.3892/or.2014.3300. Epub 2014 Jul 2.

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.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Glypicans / genetics*
  • Glypicans / metabolism*
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Transgenic
  • Neoplasms, Experimental
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Spleen / cytology

Substances

  • GPC3 protein, mouse
  • Glypicans