Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model

  • Authors:
    • Keisuke Okudaira
    • Ryota Hokari
    • Yoshikazu Tsuzuki
    • Yoshikiyo Okada
    • Shunsuke Komoto
    • Chikako Watanabe
    • Chie Kurihara
    • Atsushi Kawaguchi
    • Shigeaki Nagao
    • Miyuki Azuma
    • Hideo Yagita
    • Soichiro Miura
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/ijo_00000387
  • Pages: 741-749
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Abstract

The negative signal provided by interactions of programmed death-1 (PD-1) and its ligands, B7-H1 and B7-DC, has been suggested to play an important role in tumor evasion from host immunity. Pancreas cancer patients with B7-H1 expression have a poor prognosis. B7-H1 blocking has been shown to inhibit the development of a subcutaneous tumor from a pancreas cancer cell line. In this study, we investigated the effects of B7-DC as well as B7-H1 blockade in vivo in a murine pancreatic cancer model. Pancreatic cancer cells (Panc02) were inoculated in the pancreas of C57BL/6 mice. Five weeks later, tumor sizes were measured and the mice bearing appropriate size of tumors received the following treatments. Blocking antibodies against B7-H1 or B7-DC (200 µg) were administered 3 times/week for 3 weeks. Cells infiltrating the tumors were characterized by immunohistochemistry. Effects of antibodies on cytokine and FoxP3 expression were examined by quantitative RT-PCR. In vitro cultured Panc02 cells expressed B7-H1 upon IFN-γ stimulation. However, expression of B7-H1 and B7-DC was found mainly on CD45-positive infiltrating cells and rarely on cancer cells in vivo. Treatment with both antibodies significantly decreased tumor growth in vivo. B7-DC blockade decreased the levels of IL-10 and FoxP3, suggesting that regulatory systems are mainly inhibited at the tumor site. B7-H1 blockade increased the levels of IFN-γ and FoxP3. Collectively, blocking of B7-H1 or B7-DC efficiently induced regression of pre-established pancreatic cancers by up-regulating IFN-γ production and down-regulating IL-10 production at the tumor site.

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October 2009
Volume 35 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Okudaira K, Hokari R, Tsuzuki Y, Okada Y, Komoto S, Watanabe C, Kurihara C, Kawaguchi A, Nagao S, Azuma M, Azuma M, et al: Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model. Int J Oncol 35: 741-749, 2009
APA
Okudaira, K., Hokari, R., Tsuzuki, Y., Okada, Y., Komoto, S., Watanabe, C. ... Miura, S. (2009). Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model. International Journal of Oncology, 35, 741-749. https://doi.org/10.3892/ijo_00000387
MLA
Okudaira, K., Hokari, R., Tsuzuki, Y., Okada, Y., Komoto, S., Watanabe, C., Kurihara, C., Kawaguchi, A., Nagao, S., Azuma, M., Yagita, H., Miura, S."Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model". International Journal of Oncology 35.4 (2009): 741-749.
Chicago
Okudaira, K., Hokari, R., Tsuzuki, Y., Okada, Y., Komoto, S., Watanabe, C., Kurihara, C., Kawaguchi, A., Nagao, S., Azuma, M., Yagita, H., Miura, S."Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model". International Journal of Oncology 35, no. 4 (2009): 741-749. https://doi.org/10.3892/ijo_00000387