Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in the dendritic cell-based vaccine.

OHSHIO, Yasuhiko

doi:https://doi.org/10.1111/cas.12584

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アイテム

Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in the dendritic cell-based vaccine.

http://hdl.handle.net/10422/10591

名前 / ファイル	ライセンス	アクション
cas12584.pdf (1.7 MB)

Item type

学位論文 / Thesis or Dissertation(1)

公開日

2015-07-24

タイトル

Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in the dendritic cell-based vaccine.

言語

eng

キーワード

言語

主題Scheme

Other

主題

Cancer-associated fibroblasts

キーワード

言語

主題Scheme

Other

主題

dendritic cell-based vaccine immunotherapy

キーワード

言語

主題Scheme

Other

主題

suppressor immune cells

キーワード

言語

主題Scheme

Other

主題

tranilast

キーワード

言語

主題Scheme

Other

主題

tumor microenvironment

資源タイプ

資源タイプ識別子

http://purl.org/coar/resource_type/c_db06

資源タイプ

doctoral thesis

アクセス権

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

著者

OHSHIO, Yasuhiko

抄録

内容記述タイプ

Abstract

内容記述

Given the close interaction between tumor cells and stromal cells in the tumor microenvironment (TME), TME-targeted strategies would be promising for developing integrated cancer immunotherapy. Cancer-associated fibroblasts (CAFs) are the dominant stromal component, playing critical roles in generation of the pro-tumorigenic TME. We focused on the immunosuppressive trait of CAFs, and systematically explored the alteration of tumor-associated immune responses by CAF-targeted therapy. C57BL/6 mice s.c. bearing syngeneic E.G7 lymphoma, LLC1 Lewis lung cancer, or B16F1 melanoma were treated with an anti-fibrotic agent, tranilast, to inhibit CAF function. The infiltration of immune suppressor cell types, including regulatory T cells and myeloid-derived suppressor cells, in the TME was effectively decreased through reduction of stromal cell-derived factor-1, prostaglandin E2 , and transforming growth factor-β. In tumor-draining lymph nodes, these immune suppressor cell types were significantly decreased, leading to activation of tumor-associated antigen-specific CD8(+) T cells. In addition, CAF-targeted therapy synergistically enhanced multiple types of systemic antitumor immune responses such as the cytotoxic CD8(+) T cell response, natural killer activity, and antitumor humoral immunity in combination with dendritic cell-based vaccines; however, the suppressive effect on tumor growth was not observed in tumor-bearing SCID mice. These data indicate that systemic antitumor immune responses by various immunologic cell types are required to bring out the efficacy of CAF-targeted therapy, and these effects are enhanced when combined with effector-stimulatory immunotherapy such as dendritic cell-based vaccines. Our mouse model provides a novel rationale with TME-targeted strategy for the development of cell-based cancer immunotherapy.

言語

内容記述

内容記述タイプ

Other

内容記述

雑誌掲載時のタイトル: Cancer-associated　fibroblast-targeted strategy enhances antitumor immune responses in dendritic cell-based vaccine

言語

学位名

言語

学位名

博士（医学）

学位授与機関

学位授与機関識別子Scheme

kakenhi

学位授与機関識別子

14202

言語

学位授与機関名

滋賀医科大学

学位授与年度

内容記述タイプ

Other

内容記述

平成26年度

言語

学位授与年月日

2015-03-10

学位授与番号

甲第728号

書誌情報

en : Cancer science

巻 106, 号 2, p. 134-142, 発行日 2015-01-16

出版者

Japanese Cancer Association

言語

NCID

収録物識別子タイプ

NCID

収録物識別子

AA11808050

権利

権利情報

著者版フラグ

出版タイプResource

http://purl.org/coar/version/c_970fb48d4fbd8a85

ISSN

収録物識別子タイプ

PISSN

収録物識別子

1347-9032

PMID

識別子タイプ

PMID

Versions

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2023-06-19 12:10:12.653784

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Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in the dendritic cell-based vaccine.

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