Tanaka, Nobuyuki

写真a

Affiliation

School of Medicine, Department of Urology (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

External Links
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Academic Background 【 Display / hide 】

  • 1996.04
    -
    2003.03

    慶應義塾大学, 医学部

    Graduated

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Academic Degrees 【 Display / hide 】

  • 医学博士, Keio University, 2015.02

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Papers 【 Display / hide 】

  • Clonal diversity shapes the tumour microenvironment leading to distinct immunotherapy responses in metastatic urothelial carcinoma.

    Kamatani T, Umeda K, Iwasawa T, Miya F, Matsumoto K, Mikami S, Hara K, Shimoda M, Suzuki Y, Nishino J, Kato M, Kakimi K, Tanaka N, Oya M, Tsunoda T

    Nature communications 16 ( 1 ) 7995 2025.08

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    Repeated oncogenic mutations and polyclonal proliferation are evident in cancers. However, little is known about the polyclonal principles governing the systemic cancerous lineage during immunotherapy. Here, we examine a unique autopsy case of metastatic urothelial carcinoma that exhibits different treatment responses to anti-PD-1 therapy at each tumor site. By performing in-depth analyses of different multiregional bulk tumor masses, we reveal that subsets of subclones acquire potential driver mutations under treatment selection pressure. Spatial transcriptomics analysis reveals that subclones resistant to immunotherapy form distinct immunosuppressive environments consistent with their habitats. Furthermore, different cancer hallmarks are identified in each of the subclones that expand under immunotherapy at single-cell level; for example, one subclone is more proliferative, and another is more stem-cell-like. In summary, this study provides an overall picture of the polyclonal competition and changes in the immune microenvironment that are related to resistance to immunotherapy in patients with malignancies.

  • Prognostic impact and landscape of cellular CXCR5 chemokine receptor expression in clear-cell renal cell carcinoma.

    Arai M, Tanaka N, Takamatsu K, Murakami T, Mikami S, Imamura T, Nakamura K, Nishihara H, Oya M

    Cancer immunology, immunotherapy : CII 74 ( 5 ) 166 2025.04

    ISSN  0340-7004

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    CXCR5 is a chemokine receptor that promotes B cell follicular formation and antibody production. Indeed, CXCR5 has been found to be expressed in a variety of cancers; however, the role of CXCR5 expression in clear-cell renal cell carcinoma (ccRCC) remains unclear. We aimed to determine the impact of cellular CXCR5 expression on cancer outcomes, the PD-1/PD-L1 axis, and genetic states in patients with ccRCC. First, multiplex immunofluorescence staining for CXCR5, CD4, CD8, and AE1/AE3, along with automated single-cell counting, was performed to assess cellular CXCR5 expression in ccRCC and its association with prognosis. Second, the tumour microenvironment (TME) was analysed, with a focus on the relationship between the PD-1/PD-L1 axis and CXCR5 expression. Finally, an integrated analysis of CXCR5 expression and genomic mutation information was conducted to reveal the genetic background underlying CXCR5 expression. A total of 105 ccRCC patients were included. Among the 696,964 cells analysed, the distribution of CXCR5-expressing cells was as follows: 30% CXCR5+CD4+ cells, 9% CXCR5+CD8+ cells, and 26% CXCR5+AE1/AE3+ cells. Survival analysis revealed that tumours with low-CXCR5+CD8+ cells had a poor prognosis; TME analysis revealed a relationship between low-CXCR5+CD8+ status and a highly suppressive PD-L1-positive immune environment. Genomic analysis revealed a correlation between low-CXCR5+CD8+ status and high rates of alterations in chromatin remodelling genes, including PBRM1. This study highlights the significance of CXCR5+CD8+ cells in ccRCC, demonstrating their clinical implications and revealing the immunogenomic landscape underlying CXCR5 expression.

  • Genomic characterization of metastatic patterns in prostate cancer using circulating tumor DNA data from the SCRUM-Japan MONSTAR SCREEN project.

    Shiota M, Matsubara N, Kato T, Eto M, Osawa T, Abe T, Shinohara N, Nishimoto K, Yasumizu Y, Tanaka N, Oya M, Fujisawa T, Horasawa S, Nakamura Y, Yoshino T, Nonomura N

    The journal of liquid biopsy 7   100282 2025.03

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    Purpose: Genomic characterization of the predisposition of tumors to metastasize to specific sites has been performed in a few studies using mainly tissue-derived genomes. This nationwide prospective observational study investigated the association between genomic characteristics using circulating tumor DNA (ctDNA), and the synchronous and metachronous metastasis of tumors to specific target organs in advanced prostate cancer. Methods: Patients with advanced prostate cancer undergoing systemic treatment were included. ctDNA was analyzed using the FoundationOne®Liquid CDx assay at enrollment. Associations between genomic characteristics and metastatic status were examined. Results: Alterations in the genes MYC, APC, and BRCA2 and the DNA repair, MYC, and WNT pathways were associated with lung and liver metastasis. PTEN gene alterations and PI3K pathway alteration were associated with synchronous lung metastasis. RB1 gene alteration and RAS/RAF/MAPK pathway alteration were associated with synchronous liver metastasis. RB1 and BRCA2 gene alterations predicted metachronous lung metastasis, while TP53 and MYC gene alterations predicted metachronous liver metastasis. Conclusions: This study identifies genomic alterations in ctDNA associated with synchronous and metachronous metastases. These findings may be clinically helpful for treating, managing, and monitoring cancer.

  • Predictors of Pentafecta Failure Despite Trifecta Achievement in Robot-Assisted Partial Nephrectomy

    Kamisawa K., Takeda T., Nishimoto Y., Tanigawa M., Fukumoto K., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Asanuma H., Oya M.

    Asian Journal of Endoscopic Surgery 18 ( 1 ) e70167 2025.01

    ISSN  17585902

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    Introduction: The present study examined factors preventing the achievement of pentafecta in patients who have already met trifecta criteria following robot-assisted partial nephrectomy (RAPN). Methods: A retrospective observational study was conducted on 103 patients who underwent RAPN for localized renal tumors at Keio University Hospital between 2019 and 2023. Clinical characteristics, surgical parameters, and postoperative renal function were analyzed. Multivariate logistic regression analyses were performed to identify independent predictors of trifecta and pentafecta achievement. Results: The achievement rates for trifecta and pentafecta were 88% and 27%, respectively. Independent predictors of trifecta achievement were tumor size ≤ 20 mm (OR = 5.496, p = 0.039) and estimated blood loss ≤ 50 cc (OR = 7.983, p = 0.011). Significant predictors of pentafecta achievement were age ≤ 63 years (OR = 3.753, p = 0.026) and tumor exophyticity ≥ 50% (OR = 4.054, p = 0.018). Independent predictors of pentafecta failure despite trifecta achievement were age > 63 years (OR = 0.223, 95% CI: 1.347–14.904, p = 0.014) and tumor exophyticity < 50% (OR = 0.205, 95% CI: 1.474–16.159, p = 0.009). The pentafecta failure rate was 95% in patients who achieved trifecta but had both risk factors, namely, older age and embedded tumors. Conclusion: Older age and tumor exophyticity < 50% are significant predictors of pentafecta failure despite achieving trifecta. The consideration of these factors may help refine surgical planning and postoperative management.

  • Artificial-Intelligence-based Surgical Phase Recognition in Robot-Assisted Radical Prostatectomy and Cross-Surgeon Validation

    Konnai Y., Fukumoto K., Takeuchi M., Takeuchi R., Fujiwara S., Yasumizu Y., Tanaka N., Takeda T., Matsumoto K., Kosaka T., Kawakubo H., Kitagawa Y., Oya M.

    Annals of Surgical Oncology  2025

    ISSN  10689265

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    Background: Artificial intelligence (AI) has shown potential in various fields; however, its practical application in surgery remains limited. We developed an AI system capable of automatically recognizing surgical phases in robot-assisted radical prostatectomy (RARP) and confirmed its accuracy through cross-surgeon validation. Materials and Methods: We analyzed clinical data from 102 patients who underwent RARP, including 81 consecutive patients operated on by one surgeon (surgeon A) and 21 operated on by five other surgeons (surgeons B–F). In total, 65 of the 81 patients were used for AI development, while the remaining 16, in addition to the 21 patients operated on by surgeons B–F, were used for AI validation. We classified surgical operations into nine phases. Well-trained surgeons annotated the time corresponding to each surgical phase for each video. We used Temporal Convolutional Networks for the Operating Room (TeCNO) to develop the AI model and evaluated its precision. Results: In AI development, 919,231 frames were utilized. Testing involved 216,357 frames from surgeon A and 249,553 frames from surgeons B–F. When the developed AI was used to analyze surgical videos from surgeon A, precision reached 0.94. In contrast, when the AI was applied to videos from surgeons B–F, precision was 0.83. Conclusions: The AI we developed not only showed high accuracy, but also demonstrated generalizability across different surgeons. By comprehensively evaluating surgical videos, our AI may be used to assess the quality of surgeries, thereby providing valuable feedback to surgeons and enhancing the effectiveness of surgical education.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 【泌尿器科手術ヒヤリ・ハット-トラブル対処法109の知恵】開放手術　尿失禁・骨盤臓器脱の手術　手術時にストレステストがうまくいかない

    田中 伸之, 安水 洋太, 大家 基嗣

    臨床泌尿器科 ((株)医学書院)  79 ( 4 ) 252 - 254 2025.04

    ISSN  0385-2393

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    ＜文献概要＞QTVT(あるいはTOT)手術を開始した症例.術中に300mLを膀胱に注入しストレステストを行ったが,テープの張力調整前にもかかわらず漏れない.

  • 【臨床腎・泌尿器癌(中)-基礎・臨床研究の進歩-】膀胱癌の特徴　膀胱癌の発症・進展メカニズム

    田中 伸之

    日本臨床 ((株)日本臨床社)  82 ( 増刊9 臨床腎・泌尿器癌(中) ) 23 - 27 2024.11

    ISSN  0047-1852

  • 画像診断と病理　肉腫様腎癌(淡明細胞型腎細胞癌由来)

    池田 織人, 秋田 大宇, 陣崎 雅弘, 大家 基嗣, 田中 伸之, 新井 恵吏

    画像診断 ((株)Gakken)  44 ( 8 ) 748 - 749 2024.06

    ISSN  0285-0524

  • 【薬の使い方がすぐわかる　泌尿器科処方ガイド】腫瘍　抗がん薬の副作用対策　急性過敏性反応

    水野 隆一, 田中 伸之, 大家 基嗣

    臨床泌尿器科 ((株)医学書院)  78 ( 4 ) 208 - 211 2024.04

    ISSN  0385-2393

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    ＜文献概要＞処方のポイント　●アナフィラキシー治療の要はアドレナリンである.●アドレナリン投与時に注意すべき症例がある.●注入時反応(IRR)予防目的に前投薬が用いられる.

  • 【前立腺肥大症:近年の治療の進歩】接触式レーザー蒸散術(Contact laser Vaporization of the Prostate:CVP)の現状と展望

    田中 伸之, 大家 基嗣

    Prostate Journal (医学図書出版(株))  10 ( 2 ) 145 - 150 2023.10

    ISSN  2188-4978

    　View Summary

    前立腺肥大症への接触レーザー蒸散術(CVP)は,光ファイバーを通して980nmダイオードレーザーを照射し,肥大した前立腺組織を気化させる。本邦では人口の高齢化に伴い,抗血栓療法を受ける患者数は増加傾向にある。ダイオードレーザーの有する蒸散力・止血能によって,抗血栓療法の休薬が難しい症例でも,安全な手術が可能となった。われわれは,抗血栓療法下のCVP安全性と有効性を評価した前向き観察研究を中心に,CVP治療の現状と展望について述べる。(著者抄録)

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Presentations 【 Display / hide 】

  • 新規分子イメージングによる腎がんPathomicsの実現:組織透明化とナノレゾリューション

    田中 伸之

    第112回日本泌尿器科学会総会, 

    2025.04

  • Novel Diagnostic of Prostate Cancer Using Urine-Derived Exosomes: Prospective Pilot Study

    田中 伸之

    The 13rd European Congress of Andrology, 

    2024.09

  • 組織透明化：がんの可視化、基礎と実践

    田中 伸之

    第49回組織細胞化学講習会, 

    2024.08

  • Whole-body analysis of clonal trajectories and spatial transcriptomics reveals inter- and intra-organ heterogeneity in urothelial carcinoma under immunotherapy

    田中 伸之

    第111回日本泌尿器科学会総会, 

    2024.04

  • 尿由来エクソソームを用いた尿路上皮癌の新しい体外診断

    田中 伸之

    第61回日本癌治療学会学術集会, 

    2023.10
    , 

    Symposium, workshop panel (nominated)

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

  • 立位CTを用いた重力下での人体の解析と未来医療への応用

    2025.04
    -
    2029.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 基盤研究(B) , Coinvestigator(s)

  • ３次元空間シングルセル解析による腎癌免疫微小環境の解明

    2025.04
    -
    2028.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 基盤研究(C), Coinvestigator(s)

  • 免疫治療下の泌尿器がん3次リンパ様構造の空間オミックス解析とバイオマーカー創出

    2025.04
    -
    2028.03

    MEXT,JSPS, 科学研究費助成事業, 基盤研究(B) , Principal investigator

  • 間質性膀胱炎の低侵襲体外診断用医薬品の開発

    2025.04
    -
    2026.03

    日本医療研究開発機構, 令和７年度橋渡し研究プログラム, Principal investigator

  • がん免疫治療下における間質軌跡地図の空間解析と新しい間質リプログラミング法の確立

    2024.07
    -
    2028.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 挑戦的研究(開拓), Principal investigator

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Awards 【 Display / hide 】

  • 慶應医学賞 ライジング・スター賞

    2025

  • 公益財団法人武田科学振興財団医学系研究継続助成

    2025

  • 慶應義塾学事振興資金（個人研究, A）

    2025

  • 第111回日本泌尿器科学会総会総会総会賞（尿路上皮腫瘍：基礎）

    2024

  • 公益財団法人安田記念医学財団癌研究助成

    2024

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, UROLOGY

    2025

  • LECTURE SERIES, UROLOGY

    2024

  • LECTURE SERIES, UROLOGY

    2023

  • LECTURE SERIES, UROLOGY

    2022

  • LECTURE SERIES, UROLOGY

    2021

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Committee Experiences 【 Display / hide 】

  • 2023.12
    -
    Present

    日本癌治療学会, 幹事

  • 2023.08
    -
    Present

    日本癌治療学会, 学術枠代議員

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