Details of a Researcher - Tanaka, Nobuyuki

Tanaka, Nobuyuki

写真a

Affiliation: School of Medicine, Department of Urology (Shinanomachi)

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

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Academic Background 【 Display / hide 】

1996.04

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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 】

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.
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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
- Access to Document (DOI)
Prognostic significance of circulating tumor DNA alterations in advanced renal cell carcinoma from SCRUM-Japan MONSTAR-SCREEN: a nationwide genomic profiling project: Genetics and Genomics

Kato T., Shiota M., Nishimoto K., Matsubara N., Osawa T., Abe T., Yasumizu Y., Tanaka N., Yamamoto Y., Ishizuya Y., Abutani H., Bando H., Fujisawa T., Nakamura Y., Oya M., Shinohara N., Eto M., Yoshino T., Nonomura N.

British Journal of Cancer 2025

ISSN 00070920

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Background: Circulating tumor DNA (ctDNA) is a promising tool for diagnosing and predicting cancer prognosis. However, its clinical utility in metastatic renal cell carcinoma (mRCC) remains unclear, particularly in terms of clinical prognosis. Methods: We enrolled 124 patients with mRCC in the MONSTAR-SCREEN study (UMIN 000036749) between August 2019 and February 2022, a national observational ctDNA-based screening study, and performed ctDNA sequencing before and at the time of resistance to systemic therapy. Results: ctDNA were assessed in 178 samples containing 432 mutations. The most frequently altered genes at baseline were VHL (25.0%), PBRM1 (10.9%), TERT2 (8.7%), BAP1 (8.7%), and MTOR (7.6%). Patients receiving first-line therapy with tumor fraction (TF) < 1.2% showed significantly better progression-free survival than those with TF ≥ 1.2% (Hazard ratio (HR) = 0.467; 95% CI 0.229–0.979; p = 0.0425). BAP1 mutational status of ctDNA at baseline led to poor OS (HR = 0.4867; 95% CI 0.322–0.736; p = 0.0003). Serial ctDNA analysis showed that 46.8% of patients developed new ctDNA mutations at disease progression, which was linked to shorter time to progression (p = 0.046). Conclusions: Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment.
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Prediction of pathological up-staging after radical nephroureterectomy in patients with upper tract urothelial carcinoma

Shojo K., Takeda T., Akita H., Suzuki T., Mikami S., Shigeta K., Yasumizu Y., Tanaka N., Matsumoto K., Morita S., Kosaka T., Mizuno R., Asanuma H., Jinzaki M., Oya M.

World Journal of Urology (World Journal of Urology) 42 ( 1 ) 192 2024.12

ISSN 07244983

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Purpose: The diagnostic accuracy of computed tomography urography for upper tract urothelial carcinoma is high; however, difficulties are associated with precisely assessing the T stage. Preoperative tumor staging has an impact on treatment options for upper tract urothelial carcinoma. We herein attempted to identify preoperative factors that predict pathological tumor up-staging, which will facilitate the selection of treatment strategies. Materials and methods: We retrospectively identified 148 patients with upper tract urothelial carcinoma who underwent computed tomography urography preoperatively followed by radical nephroureterectomy without preoperative chemotherapy at our institution between 2000 and 2021. Preoperative factors associated with cT2 or lower to pT3 up-staging were examined using a multivariate logistic regression analysis. Results: Ninety out of 148 patients were diagnosed with cT2 or lower, and 22 (24%) were up-staged to pT3. A multivariate analysis identified a positive voided urine cytology (HR 4.69, p = 0.023) and tumor length ≥ 3 cm (HR 6.33, p = 0.003) as independent predictors of pathological tumor up-staging. Conclusions: Patients diagnosed with cT2 or lower, but with preoperative positive voided urine cytology and/or tumor diameter ≥ 3 cm need to be considered for treatment as cT3.
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Prediction of undetectable circulating tumor DNA by comprehensive genomic profiling assay in metastatic prostate cancer: 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.

World Journal of Urology 42 ( 1 ) 526 2024.12

ISSN 07244983

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Background: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer. Patients and methods: Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne®Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed. Results: The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71–108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10 ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present. Conclusions: An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood.
- Access to Document (DOI)

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

Single-cell RNA-seq reveals details of BCG-refractory bladder cancer

Tanaka, Nobuyuki

科学研究費補助金研究成果報告書 2022
Integrated analysis of ITH in drug resistant prostate cancer by single cell analysis

Tanaka, Nobuyuki

科学研究費補助金研究成果報告書 2022
Establishment of new single-cell analysis platform for in-situ-visualizing genitourinary cancer.

Tanaka, Nobuyuki

学事振興資金研究成果実績報告書 (慶應義塾大学) 2022
Targeting cancer stem cells and spatial niches in kidney cancer : unravelling intratumoral heterogeneity

Tanaka, Nobuyuki

科学研究費補助金研究成果報告書 2021
Establishment of new single-cell analysis platform for in-situ-visualizing genitourinary cancer

Tanaka, Nobuyuki

学事振興資金研究成果実績報告書 (慶應義塾大学) 2021

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Reviews, Commentaries, etc. 【 Display / hide 】

【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

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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)
【どこまで変わるの?　腎細胞癌診療の進歩】診断　腎細胞癌の免疫微小環境

田中伸之, 大家基嗣

臨床泌尿器科 ((株)医学書院) 77 ( 5 ) 322 - 326 2023.04

ISSN 0385-2393

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＜文献概要＞ポイント　・「複合がん免疫療法」の成功に免疫微小環境の理解は欠かせない.・腎細胞癌の免疫微小環境は,ほかの免疫感受性腫瘍と異なり,「腫瘍内のCD8+T細胞密度の高いほうが予後が悪い」という点で異質性が際立つ.・腎細胞癌の遺伝子変異は挿入・欠失が多いため,ネオアンチゲン増加と関連するTMBが,通常は低く推定される.

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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
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Symposium, workshop panel (nominated)

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

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

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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

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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

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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
透析患者に発生する腎細胞癌のOmics解析と腫瘍免疫微小環境の統合的理解

2024.04

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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)
泌尿器がんのクローン進化と腫瘍間質の空間解析による免疫治療耐性メカニズムの解明

2024.04

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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(A) , Coinvestigator(s)