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

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      Glypican-3 (GPC3) is specifically expressed in ovarian clear cell carcinoma (OCCC), hepatocellular carcinoma (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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          The last fifteen years have seen a reemergence of interest in cancer immunosurveillance and a broadening of this concept into one termed cancer immunoediting. The latter, supported by strong experimental data derived from murine tumor models and provocative correlative data obtained by studying human cancer, holds that the immune system not only protects the host against development of primary nonviral cancers but also sculpts tumor immunogenicity. Cancer immunoediting is a process consisting of three phases: elimination (i.e., cancer immunosurveillance), equilibrium, and escape. Herein, we summarize the data supporting the existence of each of the three cancer immunoediting phases. The full understanding of the immunobiology of cancer immunosurveillance and immunoediting will hopefully stimulate development of more effective immunotherapeutic approaches to control and/or eliminate human cancers.

            Author and article information

            [1 ]Bio-Databases Institute of Reproductive and Developmental Medicine, Nagoya 458-0818, Japan
            [2 ]Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466-8550, Japan
            [3 ]Department of Cancer Biology, Nagoya University School of Medicine, Nagoya 466-8550, Japan
            [4 ]Bell Research Center for Reproductive Health and Cancer, Nagoya 458-0818, Japan
            Author notes
            Correspondence to: Dr Kiyosumi Shibata, Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan, E-mail: shiba@
            Oncol Rep
            Oncol. Rep
            Oncology Reports
            D.A. Spandidos
            September 2014
            02 July 2014
            02 July 2014
            : 32
            : 3
            : 913-921
            24992906 4121400 10.3892/or.2014.3300 or-32-03-0913
            Copyright © 2014, Spandidos Publications

            This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.



            added an editorial note to Cancer Immunotherapy
            This article was selected by ScienceOpen Consulting Editor, Richard Gallagher, to appear in the Collection entitled Cancer Immunotherapy which can be found here 1. Why this article was chosen: This work explores the mechanism of action induced by a promising new target for immunotherapy in ovarian and liver cancer. 2. What this article shows: Glypican-3 (GPC3) expression by an ovarian tumor cell line increases the number of M1 macrophages in the tumor mass. M1 macrophages are antigen-presenting cells that migrate to draining lymph nodes where they induce a T-cell-mediated immune response to GPC3. 3. A key quote from the article: “The present study … provides supportive evidence that GPC3 is an ideal target for ovarian cancer immunotherapy.” 4. Corresponding author: Kiyosumi Shibata is Associate Professor in the Department of Obstetrics and Gynecology at the Nagoya University School of Medicine in Japan. Note: Two other selected papers in this Collection use GPC3 as a model system to investigate aspects of the anti-tumor immune response.
            2015-02-24 01:29 UTC

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