immune environment in the peritoneal cavity and development of novel immune therapy in ovarian cancer

腹膜腔免疫环境及卵巢癌新型免疫疗法的发展

• 批准号: 21592130
• 负责人: MANDAI Masaki
• 金额: $ 3.08万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592130/
• 关键词: 卵巣癌; 腹膜播種; 腫瘍免疫; PD-L1; 免疫逃避機構; 局所免疫; 包括的解析; 予後; 局所免疫環境; 化学療法; CD8T細胞; 腹腔内進展

In this study, we hypothesized that cancer cells actively alter immune environment in the peritoneal cavity I order to disseminate. By using human ovarian cancer samples as well as mouse ovarian cancer peritoneal dissemination model, we thoroughly analyzed the association between immune environment and cancer dissemination. We found that PD-L1, an immune suppressive molecule, is expressed or induced by encountering the immune cells in the peritoneal cavity. Forced expression of PD-L1 resulted in the promotion of peritoneal dissemination, while inhibition of PD-L1 inhibited it. These result indicate that, in ovarian cancers with high PD-L1 expression, this molecule could be a therapeutic target to suppress peritoneal dissemination.

在这项研究中，我们假设癌细胞主动改变腹腔内的免疫环境以进行传播。通过使用人类卵巢癌样本以及小鼠卵巢癌腹膜传播模型，我们深入分析了免疫环境与癌症传播之间的关联。我们发现PD-L1是一种免疫抑制分子，通过在腹膜腔中遇到免疫细胞而表达或诱导。 PD-L1的强制表达导致腹膜播散的促进，而PD-L1的抑制则抑制腹膜播散。这些结果表明，在PD-L1高表达的卵巢癌中，该分子可能成为抑制腹膜播散的治疗靶点。

项目成果

Activated local immunity by CC chemokine ligand 19-transduced embryonic endothelial progenitor cells suppresses metastasis of murine ovarian

CC趋化因子配体19转导的胚胎内皮祖细胞激活的局部免疫抑制小鼠卵巢转移

• 发表时间: 2010
• 期刊: Stem Cells
• 影响因子: 5.2
• 作者: Hamanishi J;Mandai M;et al
• 通讯作者: et al

Suppression of Metastatic Murine Ovarian Cancer Cells by Transduced Embryonic Progenitor Cells

• DOI: 10.1007/s12672-010-0046-2
• 发表时间: 2010-11
• 期刊: Hormones and Cancer
• 影响因子: 3
• 作者: M. Mandai;J. Hamanishi;K. Abiko;N. Matsumura;T. Baba;Y. Yoshioka;I. Konishi

Assessment and manipulation of local tumor immunity in ovarian cancer management

卵巢癌治疗中局部肿瘤免疫的评估和操作

• 发表时间: 2011
• 作者: Masaki Mandai;Junzo Hamanishi;Kaoru Abiko;Noriomi Matsumura;Tsukasa Baba;Ken Yamaguchi;Kenzo Kosaka;Ikuo Konishi
• 通讯作者: Ikuo Konishi

The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors

• DOI: 10.1016/j.clim.2011.08.013
• 发表时间: 2011-12-01
• 期刊: CLINICAL IMMUNOLOGY
• 影响因子: 8.6
• 作者: Hamanishi, Junzo;Mandai, Masaki;Konishi, Ikuo
• 通讯作者: Konishi, Ikuo

進行卵巣癌に対する化学療法によって、腫瘍局所の免疫状態が変化する

晚期卵巢癌的化疗改变了肿瘤的局部免疫状态。

• 发表时间: 2011
• 作者: 濱西潤三;万代昌紀;安彦郁;松村謙臣;馬場長;山村省吾;吉岡弓子;岡本尊子;姜賢淑;奈倉道和;小阪謙三;小西郁生
• 通讯作者: 小西郁生