2022 Fiscal Year Final Research Report
Investigation of Antitumor Effects through Natural Immune Activation in Malignant Bone and Soft Tissue Tumors
Project/Area Number |
19K16802
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | National Hospital Organization, Kyushu Cancer Center (2021-2022) Kyushu University (2019-2020) |
Principal Investigator |
Setsu Nokitaka 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 整形外科医長 (40727020)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 骨軟部腫瘍 / 肉腫 / 免疫 / 骨肉腫 / TLR4 |
Outline of Final Research Achievements |
In this experimental system using a mouse-derived osteosarcoma cell line (LM8), we examined the activation state of Toll-like receptor 4 (TLR4) and the activation of innate immunity by lipopolysaccharide (LPS) using wild-type (C3H/HeN) mice with normal TLR4 function and TLR4-deficient (C3H/HeJ) mice with impaired TLR4 function. Even in the absence of LPS stimulation, wild-type mice showed a tendency of slower tumor growth compared to the deficient mice. This difference became more pronounced with LPS administration, indicating that activation of innate immunity exerted inhibitory effects on the tumor. It was found that this inhibitory effect was mediated by CD8-positive cells, and in human samples of osteosarcoma resected from patients, a correlation was observed between CD8 infiltration and prognosis. These findings suggest the potential therapeutic effects of immune activation through natural immunity in the treatment of osteosarcoma.
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Free Research Field |
骨軟部腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
悪性骨軟部腫瘍全般において全身治療の効果が乏しく治療の選択肢が少ない状況は免疫チェックポイント阻害剤の選択肢が生まれた近年でも大きく変化していない。自然免疫の活性化が腫瘍抑制につながることを証明することにより、腫瘍の組織型や抗原性によらない免疫療法の選択肢が増えることになる。抗がん剤の選択肢も含めて治療選択肢が限られている悪性骨軟部腫瘍において新たな選択肢を提示するとともに腸内細菌叢などの宿主側の予後因子あるいは治療効果因子を探索する動機付けとなることが期待される。
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