Establishment of a new preventive strategy based on the interaction of NK cells and prostate cancer stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K11638
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Toyo University
• Principal Investigator: Yano Tomohiro 東洋大学, 健康スポーツ科学部, 教授 (50239828)
• Co-Investigator(Kenkyū-buntansha): 加藤 和則 東洋大学, 理工学部, 教授 (60233780)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 前立腺がん幹細胞 / NK細胞 / 殺細胞効果 / TRAIL/DR5 / NKG2D / MICA/MICB / 免疫チェックポイント

Outline of Final Research Achievements

Focusing on the phenotype that NK cells selectively recognize and eliminate cancer stem cells, we investigated the possibility of developing prevention and treatment methods for prostate cancer, based on this phenotype in NK cells. In study on prostate cancer prevention approach, NK cells specifically activated the TRAIL/DR5 pathway against hormone-dependent prostate cancer stem-like cells, and in study on treatment approach, hormone-independent prostate cancer stem-like cells NK cells specifically activated the NKG2D/MICA/MICB pathway, which is one of the activation receptor pathways, for prostate cancer stem-like cells (CRPC), respectively. These results strongly suggested that NK cells could specifically eliminated hormone-dependent and independent prostate cancer stem-like cells. However, it was shown that immune checkpoints are activated in CRPC cells, which are more malignant, and the cell-killing effect of NK cells is weakened.

Free Research Field

癌病態制御学

Academic Significance and Societal Importance of the Research Achievements

現在罹患者数が増加している前立腺がんはその予防法と並び、治療再発後のホルモン非依存性（CRPC）の前立腺がんの治療法の開発が急務である。本研究では前立腺がん幹細胞を標的としてNK細胞が特異的にホルモン依存性及びホルモン非依存性前立腺がん幹細胞を除去する可能性を示し、NK細胞が前立腺がん幹細胞を特異的に除去できるという性質に基づいた、新たな前立腺がん予防・治療法の可能性が示され、今後NK細胞のこの性質を強化する方法論を構築することが、新たな前立腺がん予防治療法の構築につながると推測される。