The analysis of HCC immune microenvironment after receiving various kinds of HCC treatments for the improvement of iCI treatments
| Project/Area Number |
19K08374
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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 53010:Gastroenterology-related
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| Research Institution | Kumamoto University (2020-2021)
Nagoya City University (2019) |
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Principal Investigator |
Kondo Yasuteru 熊本大学, 大学院生命科学研究部(医), 客員准教授 (70455822)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Tregs / PD-1 / iCIs / MDSCs / Granuloma / CD8 / irAE / PD-L1 / TKIs / HCC / iCI |
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| Outline of Research at the Start |
肝細胞癌(HCC)の治療として、免疫チェックポイント阻害剤（iCI）と各種HCC治療併用による高い治療成績が報告された。この要因として、各種HCC治療により、がん免疫微小環境が、iCI治療に好ましい環境へ変化することが想定される。本研究では、背景肝疾患別に、各種HCC治療によるがん免疫微小環境の変化を詳細に検討し、TKI治療などが免疫細胞へ影響を及ぼすメカニズムを解明する。更に、適切にiCIとの併用治療を行う為の基礎となる研究を行い、今後の臨床応用へと発展させたい。
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| Outline of Final Research Achievements |
We could find that the expression of FoxP3 was significantly decreased after the treatment of sorafenib by using deep-sequencing analysis and PBMCs from HCC patients. Then, we carried out immune subsets analysis by using multi-color FACS. We could find that Tregs and MDSCs were significantly decreased after the treatment of sorafenib and Th1 cells was significantly increased after the treatment of sorafenib. Moreover, we demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis by anti-PD-1 therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌に対して代表的なTKIであるSorafenibを使用した際にiCIs治療の効果が増強しうる免疫環境に変化することがわかった。現在、様々なiCIs治療のコンビネーションやSequential治療が試みられているが、その際の治療判断の一助になると思われる。また、iCIs治療を行なった際の肝障害に特徴的な肝病理学的組織像も明らかとなったため、早期にステロイド投与の要否の判断が可能となり、より安全にiCIs治療が行えるようになると思われる。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Identification of microRNA-96-5p as a postoperative, prognostic microRNA predictor in non-viral hepatocellular carcinoma2022
Author(s)
Matsui T, Hamada TS, Naito Y, Nojima M, Iio E, Tamori A, Kubo S, Ide T, Kondo Y, Eguchi Y, Komori A, Morine Y, Shimada M, Utsunomiya T, Kimura K, Hiasa Y, Ochiya T, Naiki A, Takahashi S, Tanaka Y
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Journal Title
Hepatol Res.
Volume: 52(1)
Issue: 1
Pages: 93-104
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Long-term efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A multicenter retrospective study2022
Author(s)
Kawaratani H, Kondo Y, Tatsumi R, Kawabe N, Tanabe N, Sakamaki A, Okumoto K, Uchida Y, Endo K, Kawaguchi T, Oikawa T, Ishizu Y, Hige S, Takami T, Terai S, Ueno Y, Mochida S, Takikawa Y, Torimura T, Matsuura T, Ishigami M, Koike K, Yoshiji H
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Journal Title
J Clin Med.
Volume: 11(6)
Issue: 6
Pages: 1571-1571
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Establishing Efficient Systems through Electronic Medical Records to Promote Intra-hospital Referrals of Hepatitis Virus Carriers to Hepatology Specialists: A Multicenter Questionnaire-based Survey of 1,281 Healthcare Professionals2021
Author(s)
Hidaka I, Enomoto M, Sato S, Suetsugu A, Matono T, Ito K, Ogawa K, Inoue J, Horino M, Kondo Y, Sakaida I, Korenaga M.
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Journal Title
Internal Medicine
Volume: 60
Issue: 3
Pages: 337-343
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2021-02-01
Related Report
Peer Reviewed
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[Journal Article] Transcriptomics Identify Thrombospondin-2 as a Biomarker for Nonalcoholic Steatohepatitis and Advanced Liver Fibrosis2021
Author(s)
Kozumi K, Kodama T, Murai H, Sakane S, Govaere O, Cockell S, Motooka D, Kakita N, Yamada Y, Kondo Y, Tahata Y, Yamada R, Hikita H, Sakamori R, Kamada Y, Daly KA, Anstee MQ, Tatsumi T, Morii E, Takehara T
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Journal Title
Hepatology
Volume: 74(5)
Issue: 5
Pages: 2452-2466
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Proposal of Stroop test cut-off values as screening for neuropsychological impairments in cirrhosis: A Japanese multicenter study2021
Author(s)
Kondo Y, Iwasa M, Kawaratani H, Miyaaki H, Hanai T, Kon K, Hirano H, Shimizu M, Yoshiji H, Okita K, Koike K.
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Journal Title
Hepatol Res.
Volume: -
Issue: 6
Pages: 674-681
DOI
Related Report
Peer Reviewed
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[Journal Article] Pilot study of tenofovir disoproxil fumarate and pegylated interferon-alpha 2a add-on therapy in Japanese patients with chronic hepatitis B2020
Author(s)
Matsumoto A, Nishiguchi S, Enomoto H, Tanaka Y, Shinkai N, Okuse C, Kang JH, Matsui T, Miyase S, Yatsuhashi H, Nagaoka S, Kanda T, Enomoto M, Yamada R, Hiramatsu N, Saito S, Takaguchi K, Ito K, Masaki T, Morihara D, Tsuge M, Chayama K, Ikeda F, Kagawa T, Kondo Y, Murata K, Tanaka E.
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Journal Title
J Gastroenterol.
Volume: 55(10)
Issue: 10
Pages: 977-989
DOI
Related Report
Peer Reviewed
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