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Anti-CTLA-4 treatment suppresses hepatocellular carcinoma growth through Th1-mediated cell cycle arrest and apoptosis.
Morihara, Hitomi; Yamada, Tomomi; Tona, Yumi; Akasaka, Marina; Okuyama, Hirohisa; Chatani, Natsumi; Shinonome, Satomi; Ueyama, Azumi; Kuwabara, Kenji; Fujio, Yasushi.
Afiliación
  • Morihara H; Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
  • Yamada T; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Tona Y; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Akasaka M; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Okuyama H; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Chatani N; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Shinonome S; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Ueyama A; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Kuwabara K; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
  • Fujio Y; Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Osaka, Japan.
PLoS One ; 19(8): e0305984, 2024.
Article en En | MEDLINE | ID: mdl-39106430
ABSTRACT
Inhibiting the cytotoxic T-lymphocyte-associated protein-4 (CTLA-4)-mediated immune checkpoint system using an anti-CTLA-4 antibody (Ab) can suppress the growth of various cancers, but the detailed mechanisms are unclear. In this study, we established a monoclonal hepatocellular carcinoma cell line (Hepa1-6 #12) and analyzed the mechanisms associated with anti-CTLA-4 Ab treatment. Depletion of CD4+ T cells, but not CD8+ T cells, prevented anti-CTLA-4 Ab-mediated anti-tumor effects, suggesting dependence on CD4+ T cells. Anti-CTLA-4 Ab treatment resulted in recruitment of interferon-gamma (IFN-g)-producing CD4+ T cells, called T-helper 1 (Th1), into tumors, and neutralization of IFN-g abrogated the anti-tumor effects. Moreover, tumor growth suppression did not require major histocompatibility complex (MHC)-I or MHC-II expression on cancer cells. In vitro studies showed that IFN-g can induce cell cycle arrest and apoptosis in tumor cells. Taken together, these data demonstrate that anti-CTLA-4 Ab can exert its anti-tumor effects through Th1-mediated cell cycle arrest and apoptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Apoptosis / Carcinoma Hepatocelular / Células TH1 / Antígeno CTLA-4 / Puntos de Control del Ciclo Celular / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Apoptosis / Carcinoma Hepatocelular / Células TH1 / Antígeno CTLA-4 / Puntos de Control del Ciclo Celular / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos