Kurebayashi, Yutaka

写真a

Affiliation

School of Medicine, Department of Pathology （Shinanomachi）

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Career 【 Display / hide 】

  • 2022.04
    -
    Present

    Keio University School of Medicine, Department of Pathology, Assistant Professor

  • 2017.04
    -
    2022.03

    Keio University School of Medicine, Department of Pathology, Instructor/Research Associate

  • 2018.09
    -
    2020.09

    National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA, Molecular Imaging Branch, Postdoctoral Fellow

  • 2018.04
    -
    2018.09

    National Hospital Organization Saitama Hospital, Department of Pathology, Pathologist

  • 2016.04
    -
    2016.09

    Kawasaki City Kawasaki Hospital, Department of Pathology, Pathologist

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Academic Background 【 Display / hide 】

  • 2005.04
    -
    2011.03

    Keio University, School of Medicine, 医学科

    University, Graduated

  • 2013.04
    -
    2017.03

    Keio University, School of Medicine (Ph.D. course), 病理学専攻

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）/Ph.D., Keio University, Coursework, 2017.03

  • 学士（医学）/M.D., Keio University, 2011.03

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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 2011.03

  • 死体解剖資格, 2015.07

  • 日本病理学会認定病理専門医, 2017.08

  • 日本臨床細胞学会認定細胞診専門医, 2021

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Research Areas 【 Display / hide 】

  • Life Science / Human pathology

  • Life Science / Experimental pathology

  • Life Science / Immunology

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Papers 【 Display / hide 】

  • Comparative Immunohistochemical Analysis of Clinicopathological Subgroups in Hepatocellular Carcinomas from Japan and Indonesia

    Effendi K., Rahadiani N., Stephanie M., Kurebayashi Y., Tsujikawa H., Jasirwan C.O.M., Syaiful R.A., Sakamoto M.

    Journal of Clinical and Experimental Hepatology （Journal of Clinical and Experimental Hepatology)  14 （ 6 ） 101451 2024.11

    ISSN  09736883

    　View Summary

    Background: Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia. Methods: Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/β-catenin (W/B) signaling-related molecules (β-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC). Results: Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both P < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, P = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, P = 0.005). No significant differences were found in the proportions of B/S, W/B, and −/− subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and −/− subgroups (90%), whereas Japanese VETC cases (10%, P = 0.030) were nonviral (100%) and W/B subgroups (75%). Conclusion: IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.

  • Glomus Tumor of Intrathoracic Chest Wall: a Case Report

    Ishiguro Y., Masai K., Sugino K., Yano K., Nomura R., Okubo Y., Kaseda K., Hishida T., Asakura K., Kurebayashi Y., Minami Y.

    Japanese Journal of Lung Cancer （Japanese Journal of Lung Cancer)  64 （ 3 ） 208 - 209 2024.06

    ISSN  03869628

  • Tumor steatosis and glutamine synthetase expression in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy.

    Kurebayashi Y, Tsujikawa H, Sugimoto K, Yunaiyama D, Araki Y, Saito K, Takahashi H, Kakegawa T, Wada T, Tomita Y, Abe M, Yoshimasu Y, Takeuchi H, Hirata T, Sakamaki K, Kakimi K, Nagao T, Itoi T, Sakamoto M

    Hepatology research : the official journal of the Japan Society of Hepatology （Hepatology Research)  53 （ 10 ） 1008 - 1020 2023.10

    ISSN  1386-6346

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    Aim: The anti-programmed death-ligand 1 antibody atezolizumab and vascular endothelial growth factor-neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first-line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early-stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy. Methods: Thirty-three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre- and posttreatment diffusion-weighted magnetic resonance imaging (MRI) with nine b values (0–1500 s/mm2), and other clinicopathologic factors were analyzed. Results: Compared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/β-catenin-activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism-related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI-determined tumor steatosis, were the most significant prognostic indicators for progression-free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre- and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS. Conclusions: The biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism-related factors, pathologically determined tumor steatosis and/or GS expression, and MRI-determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.

  • IL-15-producing splenic B cells play pathogenic roles in the development of autoimmune hepatitis.

    Fujimori S, Chu PS, Teratani T, Harada Y, Suzuki T, Amiya T, Taniki N, Kasuga R, Mikami Y, Koda Y, Ichikawa M, Tabuchi T, Morikawa R, Yamataka K, Noguchi F, Tsujikawa H, Kurebayashi Y, Sakamoto M, Kanai T, Nakamoto N

    JHEP reports : innovation in hepatology （JHEP Reports)  5 （ 7 ） 100757 2023.07

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    Background & Aims: B-cell depletion therapy with an anti-CD20 is an effective treatment strategy for patients with refractory autoimmune hepatitis (AIH). However, the mechanisms underlying B-cell action are unclear. Methods: Herein, we used the adeno-associated virus IL-12 model, in which hepatic IL-12 expression triggers liver injuries characteristic of AIH. We also analysed the clinical samples of patients with AIH. Results: B-cell depletion using anti-CD20 or splenectomy was found to improve liver functions and decrease the cytotoxic CD8+ T-cell (cytotoxic T lymphocyte [CTL]) count in the liver. This improvement was reversed by the adoptive transfer of splenic B cells derived from AAV IL-12-treated mice to splenectomised mice as it caused the hepatic CTL count to increase. RNA-sequencing analysis identified IL-15 as a key factor in pathogenic B cells, which promotes CTL expansion and subsequent migration to the liver via the CXCL9/CXCR3 axis. Indeed, IL-15 neutralisation ameliorated hepatitis by suppressing splenic and hepatic CTLs in vivo. The close distribution of B220+ B cells and CD8+ T cells in the spleen of AIH mice suggested mutual interactions. Mechanistically, IFNγ and CD40L/CD40 signalling were indispensable for the expression of IL-15 in B cells, and in vitro co-culture experiments revealed that splenic CD40L+CD8+ T cells promoted IL-15 production in B cells, which led to CTL expansion. In patients with AIH, high serum IL-15 concentration and IL-15+ B-cell counts, positively correlating with serum alanine aminotransferase levels, support translation and potential therapeutic targeting in human AIH. Conclusions: This investigation elucidated the roles of IL-15-producing splenic B cells that occur in concert with pathogenic CD8+ T cells during the development of AIH. Impact and Implications: IL-15-producing B cells were shown to exacerbate experimental AIH via cytotoxic T lymphocyte expansion. CD40L+CD8+ T cells promoted IL-15 expression in B cells, indicating the mutual interaction of both cells. High serum IL-15 concentrations, IL-15+ B-cell counts, and CD40L+IL-15Rα+CD8+ T-cell counts were confirmed in the blood of patients with AIH.

  • Immunovascular microenvironment in relation to prognostic heterogeneity of WNT/β-catenin-activated hepatocellular carcinoma.

    Matsuda K, Kurebayashi Y, Masugi Y, Yamazaki K, Ueno A, Tsujikawa H, Ojima H, Kitago M, Itano O, Shinoda M, Abe Y, Sakamoto M

    Hepatology research : the official journal of the Japan Society of Hepatology （Hepatology Research)  53 （ 4 ） 344 - 356 2023.04

    ISSN  1386-6346

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    Aim: WNT/β-catenin-activated hepatocellular carcinoma (W/B subclass HCC) is considered a molecularly homogeneous entity and has been linked to resistance to immunotherapy. However, recent studies have indicated possible heterogeneity in the immunovascular microenvironment in this subclass. We set out to test the hypothesis that specific immunovascular features might stratify W/B subclass HCCs into tumors having distinct aggressive natures. Methods: In this study, we analyzed 352 resected HCCs including 78 immunohistochemically defined W/B subclass HCCs. The density of tumor-infiltrating CD3+ T cells and the area ratio of vessels encapsulating tumor clusters (VETC) were calculated on tissue specimens. The gene expressions of angiogenic factors were measured by quantitative reverse transcription–polymerase chain reaction. Disease-free survival (DFS) was assessed using multivariable Cox regression analyses. Results: The T-cell density of W/B subclass HCCs was regionally heterogenous within tumor tissues, and focally reduced T-cell density was observed in areas with VETC. VETC-positivity (defined as VETC area ratio greater than 1%) was inversely associated with T-cell infiltration in both W/B subclass and non-W/B subclass HCCs. Fibroblast growth factor 2 (FGF2) gene expression was higher in W/B subclass than in non-W/B subclass HCCs. The VETC-positivity and low T-cell density correlated with increased expression of FGF2 in W/B subclass HCCs. Additionally, VETC-positive HCCs showed significantly shorter DFS in W/B subclass HCCs. Conclusions: In conclusion, the immune and vascular microenvironments are interrelated and are also correlated with clinicopathological heterogeneity in W/B subclass HCC. These results could inform clinical practice and translational research on the development of therapeutic stratification of HCCs.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Histopathological classification of the immune microenvironment of hepatocellular carcinoma including all clinical stages

    2021.04
    -
    2025.03

    Keio University, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, No Setting

    　View Summary

    がんに対する免疫療法の進展を受けて、肝細胞癌の免疫微小環境の分類の確立ならびに病理診断への応用が期待されている。一方で、これまでの研究は手術により切除可能な比較的早期の肝細胞癌を主な対象としており、免疫療法の対象となる切除不能進行肝細胞癌の免疫微小環境については未だに不明である。本研究では、研究代表者がこれまでに検討した外科切除可能な肝細胞癌症例に加えて進行肝細胞癌の病理解剖例を改めて詳細に解析することで、①全ての病期（前癌病変、早期肝細胞癌から切除不能進行肝細胞癌まで）における肝細胞癌の免疫微小環境の病理学的分類の確立と、②各免疫微小環境の成立機序の一端の解明を目指す。

  • Comprehensive analysis of immune microenvironment in hepatocellular carcinoma (HCC)

    2017.08
    -
    2019.03

    Japan Society for the Promotion of Science (JSPS), Grant-in-Aid for Research Activity start-up, Yutaka Kurebayashi, Grant-in-Aid for Research Activity Start-up, Principal investigator

    　View Summary

    To analyze the patterns of anti-tumor immunity against hepatocellular carcinoma (HCC), we performed multi-color immunohistochemistry to histopathologically evaluate various immune cells and analyzed the number and distribution of each type of immune cells using microscopy. Consequently, we revealed that the patterns of anti-tumor immunity against HCC can be classified into 3 patterns, among which "Immune-high pattern" was characterized by the co-infiltration of T cells and B/plasma cells and significantly associated with better prognosis after surgical resection of HCC. We also revealed how the pattern of anti-tumor immunity changes during the course of multi-step carcinogenesis of HCC.

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Awards 【 Display / hide 】

  • 日本病理学会100周年記念病理学研究新人賞

    2016.05, 日本病理学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 日本免疫学会 Young Investigator's Award

    2010.08, 日本免疫学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

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Courses Taught 【 Display / hide 】

  • GENERAL PATHOLOGY

    2024

  • DISEASES OF ORGAN SYSTEMS

    2024

  • GENERAL PATHOLOGY

    2023

  • DISEASES OF ORGAN SYSTEMS

    2023

  • GENERAL PATHOLOGY

    2022

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Memberships in Academic Societies 【 Display / hide 】

  • 日本病理学会

    　

  • 日本免疫学会

    　

  • 日本臨床細胞学会

    　

  • American Association for Cancer Research

    　
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Committee Experiences 【 Display / hide 】

  • 2024
    -
    Present

    運営委員, 肝癌症例研究会

  • 2021
    -
    Present

    学術評議員, 日本病理学会

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