Kurebayashi, Yutaka

写真a

Affiliation

School of Medicine, Department of Pathology (Shinanomachi)

Position

Instructor

Career 【 Display / hide

  • 2017.04
    -
    Present

    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

  • 2011.04
    -
    2013.03

    Fujieda Municipal General Hospital, Resident

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

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

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

 

Research Areas 【 Display / hide

  • Human pathology

  • Experimental pathology

  • Immunology

 

Papers 【 Display / hide

  • Rapid Depletion of Intratumoral Regulatory T Cells Induces Synchronized CD8 T- and NK-cell Activation and IFNγ-Dependent Tumor Vessel Regression.

    Kurebayashi Y, Olkowski CP, Lane KC, Vasalatiy OV, Xu BC, Okada R, Furusawa A, Choyke PL, Kobayashi H, Sato N

    Cancer research (Cancer Research)  81 ( 11 ) 3092 - 3104 2021.06

    ISSN  0008-5472

     View Summary

    Regulatory T cells (Tregs) are known to inhibit antitumor immunity, yet the specific mechanism by which intratumoral Tregs promote tumor growth remains unclear. To better understand the roles of intratumoral Tregs, we selectively depleted tumor-infiltrating Tregs using anti-CD25-F(ab0)2 near-infrared photoimmunotherapy. Depletion of tumor-infiltrating Tregs induced transient but synchronized IFNg expression in CD8 T and natural killer (NK) cells. Despite the small fraction of CD8 T and NK cells contained within examined tumors, IFNg produced by these CD8 T and NK cells led to efficient and rapid tumor vessel regression, intratumoral ischemia, and tumor necrosis/apoptosis and growth suppression. IFNg receptor expression on vascular endothelial cells was required for these effects. Similar findings were observed in the early phase of systemic Treg depletion in tumor-bearing Foxp3DTR mice; combination with IL15 therapy further inhibited tumor growth and achieved increased complete regression. These results indicate the pivotal roles of intratumoral Tregs in maintaining tumor vessels and tumor growth by suppressing CD8 T and NK cells from producing IFNg, providing insight into the mechanism of Treg-targeting therapies.

  • Lipofibroadenoma arising in hyperplastic thymic tissue: Possible perivascular origin of lipofibroadenoma.

    Kurebayashi Y, Hayashi Y, Emoto K, Kaseda K, Asamura H, Mukai K, Sakamoto M

    Pathology international (Pathology International)  71 ( 4 ) 275 - 277 2021.04

    ISSN  1320-5463

  • <i>TNFRSF13B</i> c.226G&gt;A (p.Gly76Ser) as a Novel Causative Mutation for Pulmonary Arterial Hypertension.

    Shinya Y, Hiraide T, Momoi M, Goto S, Suzuki H, Katsumata Y, Kurebayashi Y, Endo J, Sano M, Fukuda K, Kosaki K, Kataoka M

    Journal of the American Heart Association (Journal of the American Heart Association)  10 ( 5 ) e019245 - 4 2021.02

     View Summary

    BACKGROUND: Recently, some studies reported the pulmonary artery hypertension (PAH)–associated genes. However, a majority of patients with familial or sporadic PAH lack variants in the known pathogenic genes. In this study, we investigated the new causative gene variants associated with PAH. METHODS AND RESULTS: Whole-exome sequencing in 242 Japanese patients with familial or sporadic PAH identified a heterozygous substitution change involving c.226G>A (p.Gly76Ser) in tumor necrotic factor receptor superfamily 13B gene (TNFRSF13B) in 6 (2.5%) patients. TNFRSF13B controls the differentiation of B cell and secretion of inflammatory cytokines and may be involved in vascular inflammation. In silico structural analysis simulation demonstrated the structural instability of the N-terminal region of the protein synthesized from TNFRSF13B p.Gly76Ser variant. These suggest that the TNFRSF13B p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels. CONCLUSIONS: TNFRSF13B p.Gly76Ser variant is a candidate of novel causative gene variant for PAH.

  • Imaging of cell-based therapy using<sup>89</sup> zr-oxine ex vivo cell labeling for positron emission tomography

    Kurebayashi Y., Choyke P.L., Sato N.

    Nanotheranostics (Nanotheranostics)  5 ( 1 ) 27 - 35 2021

     View Summary

    © The author(s). With the rapid development of anti-cancer cell-based therapies, such as adoptive T cell therapies using tumor-infiltrating T cells, T cell receptor transduced T cells, and chimeric antigen receptor T cells, there has been a growing interest in imaging technologies to non-invasively track transferred cells in vivo. Cell tracking using ex vivo cell labeling with positron emitting radioisotopes for positron emission tomography (PET) imaging has potential advantages over single-photon emitting radioisotopes. These advantages include intrinsically higher resolution, higher sensitivity, and higher signal-to-background ratios. Here, we review the current status of recently developed Zirconium-89 (89Zr)-oxine ex vivo cell labeling with PET imaging focusing on its applications and future perspectives. Labeling of cells with89Zr-oxine is completed in a series of relatively simple steps, and its low radioactivity doses required for imaging does not interfere with the proliferation or function of the labeled immune cells. Preclinical studies have revealed that 89Zr-oxine PET allows high-resolution in vivo tracking of labeled cells for 1-2 weeks after cell transfer both in mice and non-human primates. These results provide a strong rationale for the clinical translation of 89Zr-oxine PET-based imaging of cell-based therapy.

  • Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features

    Maehara J., Masugi Y., Abe T., Tsujikawa H., Kurebayashi Y., Ueno A., Ojima H., Okuda S., Jinzaki M., Shinoda M., Kitagawa Y., Oda Y., Honda H., Sakamoto M.

    Hepatology Research (Hepatology Research)  50 ( 5 ) 607 - 619 2020.05

    ISSN  13866346

     View Summary

    © 2019 The Japan Society of Hepatology Aim: Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount of collagen and elastin fibers in HCC samples with the aim of clarifying the clinico-patho-radiological significance of fiber deposition in HCC. Methods: We computed the amount of collagen and elastin fibers using digital image analysis of whole-slide images of Elastica van Gieson-stained tissues from 156 surgically resected HCCs. Furthermore, we assessed the correlations between the fiber content of HCC samples and clinical, pathological, and radiological features, including immunohistochemistry-based molecular subtypes and immunosubtypes. Results: The intratumoral area ratio of collagen in HCC tissues (median 3.4%, range 0.1–22.2%) was more than threefold that of elastin (median 0.9%, range 0.1–9.0%); there was a strong positive correlation between the amounts of collagen and elastin. Higher levels of combined collagen and elastin were significantly associated with the confluent multinodular macroscopic tumor type, the absence of a fibrous capsule, intratumoral steatosis, scirrhous tumor stroma, dense inflammatory-cell infiltrates, and the biliary/stem cell markers-positive HCC subtype. The associations of higher collagen levels with radiological findings, including heterogeneous enhancement and persistent enhancement on dynamic computed tomography, were significant. In contrast, the associations of radiological findings with elastin fibers were not significant. Intratumoral fibrous stroma in HCC comprised septum-like and perisinusoidal fibrosis; these two forms represented distinct distribution patterns of fibers and fibroblasts. Conclusion: Quantitative analysis suggested that stromal fiber-rich HCCs likely represent a distinct clinico-patho-radiological entity.

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Reviews, Commentaries, etc. 【 Display / hide

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

  • 全ての病期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成立機序の解明

    2021.04
    -
    2025.03

    Keio University, 紅林 泰, Grant-in-Aid for Early-Career Scientists

  • 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.

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: Awards of National Conference, Council and Symposium

  • 日本免疫学会 Young Investigator's Award

    2010.08, 日本免疫学会

    Type of Award: Awards of National Conference, Council and Symposium

 

Courses Taught 【 Display / hide

  • GENERAL PATHOLOGY

    2021

  • DISEASES OF ORGAN SYSTEMS

    2021

  • GENERAL PATHOLOGY

    2020

  • DISEASES OF ORGAN SYSTEMS

    2020

  • GENERAL PATHOLOGY

    2019

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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