Image analysis-based subtyping of immunosuppressive tumor-immune microenvironment in pancreatic cancer tissue
| Project/Area Number |
18K15094
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Keio University |
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Principal Investigator |
Masugi Yohei 慶應義塾大学, 医学部(信濃町), 講師 (90528598)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 膵がん / 免疫療法 / 間質標的治療 / 腫瘍不均一 / Ｔリンパ球 / 腫瘍微小環境 / 腫瘍免疫 / 間質療法 / 腫瘍内不均一 / 画像解析 / 免疫抑制 / 膵癌 / 免疫 / 人体病理学 |
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| Outline of Final Research Achievements |
We established computational quantitative system to calculate tumor-infiltrating CD8+ cells in the tumor center and the tumor margin to establish the quantitative evaluation methods for the anti-tumor immune activity and for the in situ immunosuppressive activity of pancreatic cancer microenvironment. Then, we clarified clinicopathologic significances of these quantitative measurements. We further examined candidate factors/cells contributing to the immunosuppression of pancreatic cancer stroma, and focused on the desmoplastic stroma. Using multiplex immunohistochemistry-based image analyses, we identified a stroma type that showed a significant correlation with aforementioned immunosuppressive activity of pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
難治がんの代表である膵癌に対する治療が模索される中、腫瘍間質の修飾により免疫治療効果が顕著に増強されることが明らかとなりつつある。本研究は、患者組織の精緻な定量解析を用いて、ヒト膵癌における腫瘍内CD8+T細胞除去に中心的役割を果たす有力な因子として、ある特定の線維芽細胞サブタイプを見出し、この線維芽細胞サブタイプに富む膵がんは、強力な免疫抑制活性で特徴づけられる一群であることを発見した。この結果は、膵癌モデルマウスを用いた先行研究結果によって支持されるヒト組織でのエビデンスであり、免疫療法との併用を想定した間質標的治療の実現には、治療に反応する群を選定する患者層別が重要であると考えられる。
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Pathogenesis of multiple pancreatic cancers involves multicentric carcinogenesis and intrapancreatic metastasis2020
Author(s)
Fujita, Y. Matsuda, S. Sasaki, Y. Masugi, Y. Kitago, M. Yagi, H. Abe, Y. Shinoda, M. Tokino, T. Sakamoto, M. Kitagawa, Y.
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Journal Title
Cancer Sci
Volume: 111
Issue: 2
Pages: 739-748
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Characterization of spatial distribution of tumor-infiltrating CD8(+) T cells refines their prognostic utility for pancreatic cancer survival2019
Author(s)
Masugi Y, Abe T, Ueno A, Fujii-Nishimura Y, Ojima H, Endo Y, Fujita Y, Kitago M, Shinoda M, Kitagawa Y, Sakamoto M
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Journal Title
Modern Pathology
Volume: 32
Issue: 10
Pages: 1495-1507
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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