2011 Fiscal Year Final Research Report
Cancer Immunotherapy Targeting B7-DC/ B7-H1/ PD-1 interaction May Improve Tumor Microenviroment
| Project/Area Number |
21591641
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | 腫瘍免疫 / 補助シグナル / 抗体療法 |
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| Research Abstract |
B7-H1 is a co-signal to modulate immune check point expressed on both subsets of immune effector cells and cancer. B7-H1 is able to induce an anergy of CD8+ T cells through the PD-1 receptor leading to tumor growth and immune suppression. Blockade of B7-H1 with neutralizing antibody is a novel therapy which alters tumor microenvironment. The antibody blockade of this B7-H1/ PD-1 interaction may result in the alteration of immune response and tumor microenvironment preventing tumor evasion from the immune system. Materials and Methods:
BALB/ C mice were challenged with colorectal hepatic metastases and then treated with an attenuated Listeria monocytogenes(LM) vaccine platform in combination with B7-H1 blocking antibody. Mice were investigated for survival, immunological analysis with flow cytometry and in vitro assay
Results : Mice treated with B7-H1+ LM had 70% survival. The analysis of immune subsets demonstrated an increase in expression of B7-H1 on CD8+ T cells of mice treated with LM. In vitro analysis of CD8+ T cell activation showed an increase of 50% in the presence of tumor with B7-H1 blocking antibody.
Discussion : B7-H1 blockade showed increased survival by preventing the inhibitory signaling between T cells, dendritic cells and tumor.
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