EMT-mediated tumor immunosuppression and evasion of head and neck cancer stem cells in the cancer microenvironment

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09718
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kindai University (2021-2023); Nara Medical University (2020)
• Principal Investigator: Ota Ichiro 近畿大学, 奈良病院, 准教授 (00326323)
• Co-Investigator(Kenkyū-buntansha): 高橋 昭久 群馬大学, 重粒子線医学推進機構, 教授 (60275336) ; 森 英一朗 奈良県立医科大学, 医学部, 准教授 (70803659)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: EMT / がん微小環境 / がんの浸潤・転移

Outline of Final Research Achievements

We investigated how cancer cells induce Epithelial-Mesenchymal Transition (EMT) and promote cancer stem cell activation in the cancer microenvironment and how they acquire tumor immunosuppression and evasion ability. The involvement of EMT in the acquisition of immune escape capacity in the cancer microenvironment was suggested. The results indicated that EMT enhancement and PD-L1 expression are not unidirectional, but rather complex and bidirectional. Knockdown of PD-L1/PD-L2 was found to suppress EMT. These data suggested that the induction of EMT expression in cancer cells is regulated in close interrelation with tumor immunosuppression and evasion ability via PD-L1/PD-L2.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

Wntシグナル伝達経路がSnailを介してEMTを誘導することで、MT1-MMPおよびMT2-MMPを活性化させるとともに、がん細胞の浸潤・転移能を獲得させることを示した。頭頸部がん細胞においていかにしてがん微小環境がEMTを誘導し、がん幹細胞を活性化させ浸潤・転移を促しているかを、in vitroおよびin vivoのレベルで分子生物学的手法および独自の浸潤・転移モデルを用いて解明の糸口を見出した。今後、その経路の分子標的薬の開発により、一層の治療効果が期待できる。