The relationships of tumor micro environment and radiation resistance with clonal hematopoiesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16824
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Osaka University
• Principal Investigator: Tatekawa Shotaro 大阪大学, 大学院医学系研究科, 特任助教(常勤) (40816550)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 放射線治療学 / 放射線治療抵抗性 / 腫瘍微小環境 / DNA変異解析 / clonal hematopoiesis

Outline of Final Research Achievements

The current study aimed to elucidate the mechanism of clonal hematopoiesis(CH) and radiotherapy resistance. Sequence analysis of 67 patients with head and neck cancer showed that the presence of CH was a risk factor for both recurrence-free survival and local recurrence rate, as indicated by multivariate analysis including age and stage of disease. In addition, RNA-seq was performed in peripheral blood mononuclear cells with and without CH to compare gene expression, and the expression of genes that are major mediators of inflammation and immunity was higher in patients with CH. The possibility that the presence of CH may be involved in the induction of chronic inflammation was considered. Based on these results, we have created a mouse model of CH and are conducting additional analyses.

Free Research Field

放射線治療学

Academic Significance and Societal Importance of the Research Achievements

これまで放射線治療抵抗性へのアプローチとしては低酸素イメージングや線量増加などの報告が多いが、CH に伴う炎症の惹起や腫瘍微小環境の変化に着目した研究は皆無であった。本研究はその点において独自性があり、化学放射線治療を受ける頭頸部癌患者においてCH の有無が局所再発率に関与していることが判明した。今後、CH による腫瘍微小環境の変化が放射線治療抵抗性へ関与していることをコンディショナルノックアウトマウスを用いて解析予定だが、それらが解明できれば抗炎症作用をもつ薬剤の投与や血管新生阻害剤、マクロファージの遊走を阻害する薬剤など、CH を有する患者における新たな治療戦略の設計が可能となる。