2021 Fiscal Year Final Research Report
Development of prognostic diagnosis by elucidating the mechanism of cancer immunostimulation by lymph node CD169-positive macrophages
| Project/Area Number |
19K07459
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Kumamoto University (2021)
Kyoto University (2019-2020) |
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Principal Investigator |
Saito Yoichi 熊本大学, 大学院先端科学研究部(工), 特任助教 (20783567)
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| Co-Investigator(Kenkyū-buntansha) |
大西 紘二 熊本大学, 大学院生命科学研究部(医), 特任准教授 (40613378)
藤原 章雄 熊本大学, 大学院生命科学研究部(医), 講師 (70452886)
菰原 義弘 熊本大学, 大学院生命科学研究部(医), 教授 (40449921)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | マクロファージ / リンパ節 / がん免疫 / C169 / PD-L1 / MMR / コンパニオン診断 |
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| Outline of Final Research Achievements |
Analysis using CD169-DTR mice revealed that the regional lymph node CD169-positive sinus macrophages activate anti-tumor immunity mediated by CD8-positive T cells, which determines the onset of therapeutic effect of PD-(L)1 antibody drugs. Analysis of non-small cell lung cancer (417 cases), renal cancer (38 cases) resection specimens, human tumor cell lines (41 types), and human monocyte-derived macrophages showed that IFNs-derived PD-L1 expression in tumor cells can be divided into three types. The results were consistent with the companion diagnostic criteria for each cancer. Furthermore, analysis of resected colorectal cancer specimens (83 cases) showed no correlation between CD169, CD8 and mismatch repair deficiency cases.
Based on the above, we collected basic knowledge on the mechanism of therapeutic efficacy of PD-(L)1 antibody drugs involving CD169 in regional lymph nodes and the prediction of therapeutic efficacy.
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| Free Research Field |
基礎病理学
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| Academic Significance and Societal Importance of the Research Achievements |
PD-(L)1抗体薬の治療効果発現に、所属リンパ節CD169陽性洞マクロファージが賦活する腫瘍免疫が関与していることを明らかにした。CD169は非常に高額なPD-(L)1抗体薬の治療効果予測として活用できる可能性があり、より高精度な患者選択（コンパニオン診断）の開発が可能となることで、治療成績の向上による患者利益の増加と、医療費削減による社会利益をもたらす可能性がある。
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