Analysis of cancer microenvironment under the growth control by anti-tumor immune response

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19483
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Juntendo University
• Principal Investigator: TAKEDA Kazuyoshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (80272821)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: IL-23p19 / IL-23レセプター / 肺転移 / NK細胞 / IFN-γ / CD96 / CD8T細胞 / PD-1

Outline of Final Research Achievements

Cancer microenvironment, including immune environment, are composed of various cells and deeply involved in the progression, regression, and metastasis of cancer. The purpose of this study is to elucidate the biological reactions in cancer tissues changing with the progression, regression, and metastasis of the cancer. And, the ultimate goal is to develop innovative treatments that lead to the rejection of cancer by clarifying the biological condition of cancer tissue. In this study, I have reported the following findings. 1)IL-23 produced in metastatic lungs augments lung metastasis by inhibition of IFN-γ-producing NK cell induction. 2) PD-1, TIGIT, and CD96, that inhibit the immune activity, were expressed on cytotoxic CD8 T cells in cancer tissues. And, strategical suppression of these molecule-mediate signals is an effective antitumor immunotherapy.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

癌細胞と宿主細胞の網羅的遺伝子発現とクロストークの解析により、癌増殖と拒絶の場である癌組織内の総合的な生体反応を定量的かつ網羅的に明らかにする。これにより癌増殖の理解に新たな視点を与え、革新的な治療法の開発につながると考えられる。さらに、本申請研究に得られるマウス癌モデルでの網羅的遺伝子解析情報は、現在世界中で行われているヒトサンプルを用いた網羅的遺伝子解析の結果を理解する助けとなると伴に、より早く革新的な治療ターゲットを提言する手助けとなるものと期待される。