演題抄録

シンポジウム

開催概要
開催回
第51回・2013年・京都
 

がん微小環境の免疫病態の理解とその制御

演題番号 : S5-2

[筆頭演者]
河上 裕:1 
[共同演者]
徐 明利:1、谷口 智憲:1、藤田 知信:1

1:慶應義塾大学医学部 先端医科学研究所 細胞情報研究部門

 

We have been attempting to develop effective cancer immunotherapy. However, cancer vaccine has not shown strong anti-tumor effects so far. One of the reasons is immunosuppression in tumor microenvironments. Tumors and sentinel lymph nodes appear to be in immunosuppressive conditions in general. However, it varies among patients, and it may affect patients prognosis and treatment responses. Thus, further understanding of immunopathology in tumor associated microenvironments is important. We found that infiltration of CD8 + T cells in tumors was correlated with good prognosis and HLA class-I expression in cancer cells in patients with colon cancer, and was inversely correlated with FOXP3+ Treg / CD8+ T cell ratio in tumor. In a mouse tumor models, increased of immunosuppressive cytokines such as TGF-beta in tumor microenvironment reduced CD8+ T cell infiltration in tumor accompanied by increase of Treg and MDSC in tumor and sentinel lymph nodes. Therefore, immunosuppressive factors may be one of the reasons for the differential immune status of tumor microenvironments among patients. We found that constitutive activation of various signaling in human cancer cells including MAPK, STAT3, beta-catenin, and NF-kB, caused immunosuppression in tumor associated mircoenvironments partly through production of immunosuppressive cytokines and chemokines such as TGF-beta, IL6, IL10, VEGF, and CCL2, and subsequent generation of various immunosuppressive cells such as Treg, MDSC, and impaired DCs. Inhibitors against these signaling molecules were found to reverse the cancer-induced immunosuppression by acting on both cancer cells and some immune cells. These results indicate that immune status may be influenced by cancer (oncogenes-signals) induced immunosuppressive cytokine cascades, and signal inhibitors, together with their direct antitumor effects, may be useful for combination treatment with various immunotherapies.

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