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

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 microg) 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-gamma 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-gamma and FoxP3. Collectively, blocking of B7-H1 or B7-DC efficiently induced regression of pre-established pancreatic cancers by up-regulating IFN-gamma production and down-regulating IL-10 production at the tumor site.

journal_name

Int J Oncol

authors

Okudaira K,Hokari R,Tsuzuki Y,Okada Y,Komoto S,Watanabe C,Kurihara C,Kawaguchi A,Nagao S,Azuma M,Yagita H,Miura S

doi

10.3892/ijo_00000387

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

741-9

issue

4

eissn

1019-6439

issn

1791-2423

journal_volume

35

pub_type

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