Analysis of fibrosis of cancer stroma in the hepatobiliary and pancreatic tumors.
Project/Area Number |
20K08996
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
|
Research Institution | Doshisha University |
Principal Investigator |
Iwaisako Keiko 同志社大学, 生命医科学部, 教授 (70625300)
|
Co-Investigator(Kenkyū-buntansha) |
趙 向東 京都大学, ウイルス・再生医科学研究所, 特定助教 (00444464)
瀬尾 智 京都大学, 医学研究科, 客員研究員 (70646546)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
|
Keywords | 線維化 / 肝内胆管癌 / 癌免疫 / 腫瘍浸潤リンパ球 / 肝内胆管がん / がん |
Outline of Research at the Start |
肝胆膵領域のがん組織の多くは「がん間質の線維化」という共通した病理組織学的所見があることから、がん間質に存在する筋線維芽細胞や免疫細胞について、形態学的、分子生物学的解析を行い、その役割や相互作用を明らかにする。さらに、がん間質に豊富に存在する細胞外基質について、その由来と構成を解析し、がんの増生に与える影響について検討する。がん組織の性状を詳細に解析し、予後との関連を検証することで、バイオマーカーや治療標的を見出すことができる可能性があり、肝胆膵領域のがんの長期予後を改善することが期待される。
|
Outline of Final Research Achievements |
Hepatobiliary pancreatic cancer has a poor prognosis. Histopathologically, tumor tissues show "fibrosis of the carcinoma stroma. In this study, intrahepatic cholangiocarcinoma, a malignant tumor of hepatic origin with a high degree of fibrosis of the stroma, was analyzed immunohistologically for collagen and tumor infiltrating immune cells to examine their relationship with prognosis. The collagen was predominantly type 1 and 3, and the percentage of type 3 was higher than that of normal liver tissue. However, there was no correlation between the percentage of type 3 and prognosis. The number of infiltrating lymphocytes (CD8+ T cells, CD4+ T cells, and CD20+ B cells) was better prognosis (overall survival and recurrence-free survival) with more cells. These results suggest that cancer-specific immunity to intrahepatic cholangiocarcinoma was induced at the time of surgery and contributed to the prevention of postoperative recurrence and metastasis.
|
Academic Significance and Societal Importance of the Research Achievements |
予後不良な肝臓原発のがんである肝内胆管がんには、手術以外に有効な治療法がない。手術で切除された癌の組織を性状解析することにより、治療標的を見出し、有効な治療法開発につなげることを目的として行われた研究である。近年、新たながんの治療法として確立された免疫チェックポイント阻害薬の有効性について、薬物ががん細胞に辿り着くのを阻害すると考えられている間質の線維の状態や免疫チェックポイント阻害薬によって賦活化されるキラーT細胞の存在などを明らかにした。線維化は予後不良因子ではなく、キラーT細胞の浸潤が多いほど予後が良好であったことから、肝内胆管がんに対してもがん免疫療法が適応となる可能性がある。
|
Report
(4 results)
Research Products
(20 results)
-
-
-
[Journal Article] In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy2022
Author(s)
Okada H, Takahashi K, Yaku H, Kobiyama K, Iwaisako K, Zhao X, Shiokawa M, Uza N, Kodama Y, Ishii KJ, Seno H.
-
Journal Title
Sci Rep.
Volume: 12
Issue: 1
Pages: 2132-2132
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Immunotherapy-based targeting of MSLN + activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis2021
Author(s)
Nishio T, Koyama Y, Liu X, Rosenthal SB, Yamamoto G, Fuji H, Baglieri J, Li N, Brenner LN, Iwaisako K, Taura K, Hagood JS, LaRusso NF, Bera TK, Pastan I, Brenner DA, Kisseleva T.
-
Journal Title
PNAS
Volume: 118(29)
Issue: 29
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
[Journal Article] Cytotoxic T lymphocytes regenerated from iPS cells have therapeutic efficacy in a patient-derived xenograft solid tumor model.2020
Author(s)
Kashima S, Maeda T, Masuda K, Nagano S, Inoue T, Takeda M, Kono Y, Kobayashi T, Saito S, Higuchi T, Ichise H, Kobayashi Y, Iwaisako K, Terada K, Agata Y, Nakamura K, Saito M, Narita S, Ogawa O, Habuchi T, Kawamoto H.
-
Journal Title
iScience
Volume: 23
Issue: 4
Pages: 100998-100998
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Presentation] The association of regulatory T cells with tumor infiltrationg lymphocytes and fibrosis in non-HCC liver cancer.2021
Author(s)
Fuji H, Iwaisako K, Ohkubo S, Seo S, Taura K, Asagiri M, Sakaguchi N, Sakaguchi S, Kisseleva T, Brebber D, Hatano E.
Organizer
AASLD The Liver Meeting
Related Report
Int'l Joint Research
-
-
-
-
-
-