2022 Fiscal Year Final Research Report
Development of multimodal immunotherapeutic strategy for refractory gastrointestinal cancer
| Project/Area Number |
19H03734
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
SHO MASAYUKI 奈良県立医科大学, 医学部, 教授 (50364063)
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| Co-Investigator(Kenkyū-buntansha) |
國安 弘基 奈良県立医科大学, 医学部, 教授 (00253055)
赤堀 宇広 奈良県立医科大学, 医学部, 学内講師 (10423922)
中川 顕志 奈良県立医科大学, 医学部附属病院, 研究員 (30812341)
長井 美奈子 奈良県立医科大学, 医学部, 助教 (80646092)
高木 忠隆 奈良県立医科大学, 医学部附属病院, 研究員 (20833700)
中村 広太 奈良県立医科大学, 医学部附属病院, 研究員 (30790802)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 難治性消化器癌 / 免疫治療 / 放射線治療 / 治療抵抗性 / CD200 |
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| Outline of Final Research Achievements |
We analyzed factors associated with treatment resistance in refractory gastrointestinal cancers such as pancreatic cancer. We found that CD200 expression in tumor cells was significantly higher in patients treated with preoperative therapy than in those not treated preoperatively. Furthermore, we also found that the prognosis of the high CD200 expression group was poorer than that of the low expression group. The results also showed a significant inverse correlation with infiltrating T cells including CD4, CD8, and CD45RO.
Taken together, data suggest that CD200 is an important factor in the host immune system of various gastrointestinal cancers, and plays a critical role in treatment resistance. Therefore, CD200 may be useful as a therapeutic target molecule as well as biomarker. In addition, we succeeded in establishing a patient-derived xenograft mouse in vivo model from actual pancreatic cancer surgical specimens, which could be a useful therapeutic tool in the future.
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| Free Research Field |
消化器外科
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌等の難治性消化器癌では，化学療法が急速に進歩する今日においては，治療期間が長期化することと相まって，治療抵抗性獲得が大きな臨床課題となってきている．今回CD200が治療抵抗性獲得機構の機序の一つとして明らかとなった．今後CD200が治療抵抗性のバイオマーカーとなり，CD200標的治療が実現すれば，現行の癌治療成績は飛躍的に改善する可能性がある．さらに癌患者特異的に作成するin vivoモデルは真の個別化治療の推進につながる可能性もあり，特に治療抵抗性を示す癌患者にとっては意義が大きいものと思われる．盲目的に行う一元的な癌治療の回避は，医療経済に及ぼす影響も大きいものと期待できる．
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