Immunological mechanisms that determine the phenotype of neoplastic bone destruction

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K21058
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Osaka University
• Principal Investigator: TAKAHATA SOSUKE 大阪大学, 歯学部附属病院, 医員 (90964875)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 口腔腫瘍 / 歯肉癌 / 扁平上皮癌 / RANKL / 破骨細胞 / IL-7

Outline of Final Research Achievements

Two subtypes of SCCVII were used to create two different pathological models, low and high bone resorption types, and tumor histology was compared. Analysis of the tumor tip area in close proximity to bone revealed that the osteoclasts (TRAP-positive cells) in the high-resorption type were not only more numerous than those in the low-resorption type, but also had larger cytoplasm, were distributed outside the bone-adjacent area, and had a greater concentration of CD80-positive TRAP-positive cells derived from dendritic cells than those derived from monocytes at the tumor tip. Although there was no difference in suppressive T cells between the two types, CD4-positive T cells, which are thought to be involved in pathological osteoclast differentiation derived from dendritic cells, accumulated more in the hyperabsorptive type. This suggests that pathological bone resorption may involve osteoclasts that do not appear under physiological conditions.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

歯肉癌、歯肉原発の口腔扁平上皮癌の顎骨内への進展は破骨細胞の活性化による骨吸収が主体である。破骨細胞の積極的な誘導によって癌が顎骨を穿孔性に骨吸収する「浸潤型」と破骨細胞の誘導に乏しく緩慢に骨吸収する病態「圧迫型」に大別され、歯肉癌の骨吸収型は組織学的悪性度の指標になっている。 先行研究において、腫瘍細胞から産生される液性因子インターロイキン7 (IL-7)が浸潤型の骨吸収の出現に寄与する可能性を見出した。また本研究において腫瘍細胞由来IL-7のみならずの免疫機構の変化の詳細が明らかになることで新たな新薬開発などの臨床応用の可能性という点において非常に意義のある研究であると考える。