Education 【 display / non-display 】

Education 【 display / non-display 】

• 1978

  -

  1984

  National Defense Medical College   Medical Science  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 札幌医科大学   M.D., Ph.D.

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 1984.03

  -

  1997.11

  Japan Air Self Defense Force   Flight Surgeon

• 2015.10

  -

  Now

  Sapporo Medical University   Graduate School of Medicine   Professor

• 2015.10

  -

  Now

  Sapporo Medical University   School of Medicine Medical Sciences   Professor

• 2004.10

  -

  2015.10

  Sapporo Medical University   Graduate School of Medicine   Associate Professor

• 1997.11

  -

  2015.10

  Sapporo Medical University   School of Medicine Medical Sciences   Assistant Professor and Associate Professor

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Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 　

  　

  　

  日本宇宙生物学会

• 　

  　

  　

  Cell Stress Society International

• 　

  　

  　

  The Japanese Society of Pathology

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  The Japanese Cancer Association

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  The Japanese Society for Immunology

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Tumor biology   Cancer Stem Cell

• Life sciences   Tumor diagnostics and therapeutics   Immunotherapy, Vaccine, T-cell Therapy

• Life sciences   Cell biology   Cellular Stress Response, Stress Protein, Heat Shock Protein

• Life sciences   Experimental pathology   Cancer Stem Cell

• Life sciences   Human pathology   Immunopathology

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   Graduate School of Medicine   Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• Cancer Immunity, Immunotherapy, Vaccine, T-cell Therapy

• Autoimmunity, Autoantibody, Inflammation

• Cellular Stress Response, Heat Shock Protein, Molecular Chaperone

• Cancer Stem Cell, Oncogene, Tumor Suppressor

• Immunopathology, Human Pathology

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Distinct induction pathways of heat shock protein 27 in human keratinocytes: Heat stimulation or capsaicin through phosphorylation of heat shock factor 1 at serine 326 and/or suppression of ΔNp63.

  Terufumi Kubo, Kenta Sasaki, Sayuri Sato, Tomoyuki Minowa, Tokimasa Hida, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Hisashi Uhara, Toshihiko Torigoe

  Biochemical and biophysical research communications   708   149817 - 149817  2024.03  [International journal]

  　View Summary

  Epidermal keratinocytes, forming the outermost layer of the human body, serve as a crucial barrier against diverse external stressors such as ultraviolet radiation. Proper keratinocyte differentiation and effective responses to external stimuli are pivotal for maintaining barrier integrity. Heat is one such stimulus that triggers the synthesis of heat shock proteins (HSPs) when cells are exposed to temperatures above 42 °C. Additionally, activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) occurs at 42 °C. Here, we explore the interplay between TRPV1 signaling and HSP induction in human keratinocytes. Both heat and capsaicin, a TRPV1 agonist, induce expression of HSP27, HSP70, and HSP90 in keratinocytes. Interestingly, pharmacological inhibition of TRPV1 attenuates heat-induced HSP27 expression, but not that of HSP70 or HSP90. Furthermore, both heat and capsaicin stimulation result in distinct phosphorylation patterns of heat shock factor 1 (HSF1), with phosphorylation at serine 326 being a common feature. Notably, genetic manipulation to mimic dephosphorylation of HSF1 at serine 326 reduces HSP27 levels. Additionally, ΔNp63, a key regulator of epidermal differentiation, negatively modulates HSP27 expression independently of HSF1 phosphorylation status. While heat stimulation has no effect on ΔNp63 expression, capsaicin reduces its levels. The precise role of TRPV1 signaling in keratinocytes warrants further investigation for a comprehensive understanding of its impact on barrier function.

  DOI PubMed

• NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein.

  Aiko Murai, Terufumi Kubo, Takayuki Ohkuri, Junko Yanagawa, Yuki Yajima, Akemi Kosaka, Dongliang Li, Toshihiro Nagato, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Takeshi Nagasaki, Yoshihiko Hirohashi, Hiroya Kobayashi, Toshihiko Torigoe

  Immunological medicine     1 - 7  2024.01  [International journal]

  　View Summary

  The recognition by cytotoxic T cells (CTLs) is essential for the clearance of SARS-CoV-2 virus-infected cells. Several viral proteins have been described to be recognized by CTLs. Among them, the spike (S) protein is one of the immunogenic proteins. The S protein acts as a ligand for its receptors, and several mutants with different affinities for its cognate receptors have been reported, and certain mutations in the S protein, such as L452R and Y453F, have been found to inhibit the HLA-A24-restricted CTL response. In this study, we conducted a screening of candidate peptides derived from the S protein, specifically targeting those carrying the HLA-A24 binding motif. Among these peptides, we discovered that NF9 (NYNYLYRLF) represents an immunogenic epitope. CTL clones specific to the NF9 peptide were successfully established. These CTL clones exhibited the ability to recognize endogenously expressed NF9 peptide. Interestingly, the CTL clone demonstrated cross-reactivity with the Y453F peptide (NYNYLFRLF) but not with the L452R peptide (NYNYRYRLF). The CTL clone was able to identify the endogenously expressed Y453F mutant peptide. These findings imply that the NF9-specific CTL clone possesses the capability to recognize and respond to the Y453F mutant peptide.

  DOI PubMed

• Characterization of CD4 T-cell phenotype in human leukocyte antigen class II-positive acral melanoma.

  Nayuha Shogase, Tomoyuki Minowa, Junji Kato, Kohei Horimoto, Sayuri Sato, Tokimasa Hida, Yoshihiko Hirohashi, Toshihiko Torigoe, Hisashi Uhara

  The Journal of dermatology    2023.12  [International journal]

  DOI PubMed

• Eribulin is an immune potentiator in breast cancer that upregulates human leukocyte antigen class I expression via the induction of NOD-like receptor family CARD domain-containing 5.

  Asaka Wada, Yoshihiko Hirohashi, Goro Kutomi, Kenji Murata, Sadahiro Iwabuchi, Yuka Mizue, Aiko Murai, Daisuke Kyuno, Hiroaki Shima, Tomoyuki Minowa, Kenta Sasaki, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Munehide Nakatsugawa, Shinichi Hashimoto, Makoto Osanai, Toshihiko Torigoe, Ichiro Takemasa

  Cancer science   114 ( 12 ) 4511 - 4520  2023.12  [International journal]

  　View Summary

  Eribulin inhibits microtubule polymerization and improves the overall survival of patients with recurrent metastatic breast cancer. A subgroup analysis revealed a low neutrophil to lymphocyte ratio (NLR) (<3) to be a prognostic factor of eribulin treatment. We thus hypothesized that eribulin might be related to the immune response for breast cancer cells and we analyzed the effects of eribulin on the immune system. Immunohistochemical staining revealed that human leukocyte antigen (HLA) class I expression was increased in clinical samples after eribulin treatment. In vitro assays revealed that eribulin treatment increased HLA class I expression in breast cancer line cells. RNA-sequencing demonstrated that eribulin treatment increased the expression of the NOD-like family CARD domain-containing 5 (NLRC5), a master regulator of HLA class I expression. Eribulin treatment increased the NY-ESO-1-specific T-cell receptor (TCR) transduced T (TCR-T) cell response for New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) overexpressed breast cancer cells. The eribulin and TCR-T combined therapy model revealed that eribulin and immunotherapy using TCR-T cells has a synergistic effect. In summary, eribulin increases the expression of HLA class 1 via HLA class 1 transactivatior NLRC5 and eribulin combination with immunotherapy can be effective for the treatment of breast cancer.

  DOI PubMed

• Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum.

  Hazuki Kashiwagi, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Yoshihiko Hirohashi, Yuya Fujibe, Terufumi Kubo, Masayuki Someya, Tsuyoshi Baba, Shinichi Ishioka, Toshihiko Torigoe, Tsuyoshi Saito

  Medical molecular morphology    2023.10  [Domestic journal]

  　View Summary

  Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Rapid and efficient detection of immunogenic neoantigens using NAP-selection

  時田芹奈, 時田芹奈, 金関貴幸, 金関貴幸, 鳥越俊彦, 鳥越俊彦

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

• 化学放射線療法+免疫療法を行った3期切除不能非小細胞肺癌における,末梢血リンパ細胞のTCRレパトア解析

  染谷正則, 長谷川智一, 北川未央, 土屋高旭, 眞船翔, 後町俊夫, 池内佑太郎, 金関貴幸, 鳥越俊彦, 坂田耕一

  日本免疫治療学会学術集会プログラム・抄録集   20th  2023

  J-GLOBAL

• Characteristic vascular structure of placental villi in Placenta accreta spectrum

  柏木葉月, 久保輝文, 廣橋良彦, 鳥越俊彦

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

• 反復着床不全,不育症における慢性子宮内膜炎とマイクロビオータ

  滝本可奈子, 山田秀人, 島田茂樹, 福士義将, 和田真一郎, 水無瀬昴, 鳥越俊彦

  日本生殖医学会雑誌   68 ( 1/2 )  2023

  J-GLOBAL

• Identification and evaluation for immunogenic peptides derived from SARS-CoV-2 spike protein

  小林博也, 矢島優己, 小坂朱, 長門利純, 廣橋良彦, 鳥越俊彦, 大栗敬幸

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

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Industrial Property Rights 【 display / non-display 】

Industrial Property Rights 【 display / non-display 】

• T細胞レセプターとその利用

  鳥越 俊彦, 塚原 智英, 廣橋 良彦, 田路 真悟, 中野 一絵, 齊藤 尚吾

  Patent

  J-GLOBAL

• 腫瘍抗原ペプチド

  特許第6960179号

  佐藤 昇志, 鳥越 俊彦, 廣橋 良彦, 金関 貴幸, コーチン ビタリー, 高谷 あかり, 後藤 正志

  Patent

  J-GLOBAL

• 腫瘍抗原ペプチド

  佐藤 昇志, 鳥越 俊彦, 廣橋 良彦, 金関 貴幸, コーチン ビタリー, 高谷 あかり, 後藤 正志

  Patent

  J-GLOBAL

• 腫瘍抗原ペプチド

  特許第6960179号

  佐藤 昇志, 鳥越 俊彦, 廣橋 良彦, 金関 貴幸, コーチン ビタリー, 高谷 あかり, 後藤 正志

  Patent

  J-GLOBAL

• がん幹細胞特異的抗体

  塚原 智英, 鳥越 俊彦

  Patent

  J-GLOBAL

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• Hokkaido Scientific Technology Prize

  2023.02   Hokkaido Prefecture   腫瘍免疫病理学研究によるがんワクチン療法の開発

• The Akiyama Foundation Prize

  2022.09   The Akiyama Life Science Foundation   ヒトがん免疫応答のメカニズム解明とがん免疫療法への応用研究

• Research Grant

  2014   Ono Cancer Research Foundation  

  Winner： Torigoe Toshihiko

• Research and Development Grant

  2014   NOASTEC Foundation  

  Winner： Torigoe Toshihiko

• Academic Research Award

  2007.10   The Japanese Society of Pathology  

  Winner： Torigoe Toshihiko

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• A study of computer aided diagnosis system of cervical cytology using deep learning.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2023.04

  -

  2026.03

   

  新開 翔太, 鳥越 俊彦, 真里谷 奨, 藤野 雄一, 斉藤 豪

• Comprehensive analysis of T-cell receptor ligand by using pHLA multimer library

  Grant-in-Aid for Challenging Research (Pioneering)

  Project Year :

  2021.07

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  2025.03

   

  鳥越 俊彦, 久保 輝文

• 乳癌の転移巣を伴うリンパ節内のT-cellにおける免疫応答

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  島 宏彰, 竹政 伊知朗, 九冨 五郎, 里見 蕗乃, 和田 朝香, 鳥越 俊彦, 廣橋 良彦

  　View Summary

  本研究は、転移を来したリンパ節内のリンパ球が癌細胞を攻撃しない機序を解明することが目的である。まずはリンパ節転移巣の組織所見からリンパ球の分布と成熟の状態を調べてこれらのリンパ球の分化の把握を行い、癌微小環境におけるリンパ球の状態を位置情報の面も含めて明らかにする。そしてこれらの細胞がなぜそのような分布になっているのか、免疫チェックポイントや免疫疲弊が機序としてかかわるかどうかも解析する。最終的に臨床的経過とあわせてこれらの情報がどのような位置づけになるのか、どのように役立つのかを検討していく。

• development of combined immunotherapy targeting ero1 in triple negative breast cancer

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

  -

  2023.03

   

  九冨 五郎, 島 宏彰, 和田 朝香, 鳥越 俊彦, 廣橋 良彦, 竹政 伊知朗

  　View Summary

  現在研究のStep 1を行い、Step 2に進んでいる。具体的には、① In vivoにおけるERO1-Lα阻害剤誘導体のproof of conceptの獲得として、NOD/SCIDマウスにTN乳癌細胞株(MDA-MB231)とERO1-Lαをノックダウンした細胞株をそれぞれ接種し、マウスをERO1-Lα阻害(ERODOXIN)投与群と非投与群に分け、腫瘍が120-130mm3になったところで、投与群にERO1-Lα阻害剤誘導体を投与し、１週間後にマウスをsacrificeして、投与群と非投与群におけるVEGF-AとPD-L1の発現の変化を、western blot法と免疫染色を用い蛋白レベルで検討して一定のデータは出ている。 そして次に、② 免疫不全マウスを用いた治療実験として、NOD/SCIDマウスにTN乳癌細胞株を接種し、腫瘍のサイズが120-140mm3になったところで、治療の前日に抗原特異的CTLクローンをivする。ここでは、我々が以前より実験を行っているSurvivinのCTLクローンを用いる。マウスをPlacebo群、抗VEGF抗体投与群、抗PD-L1抗体投与群、ERO1-Lα阻害剤(ERODXIN)投与群および3剤併用群の5群に分け治療実験を行う。薬剤投与（1週間）後に腫瘍を摘出して免疫染色を行い、HIF-1α、VEGF-A、PDL1、ERO-L1αの発現量を調べている。NOD/SCIDマウスにTN乳癌細胞株のERO1-Lαをノックダウンした細胞株を接種し、腫瘍増殖能、関連蛋白の発現量を同様に調べる。ERO1-Lα阻害剤に関してはERODOXINだけでなく、我々が以前使用していたEN460も同時に用いて研究を進めている。

• Identification of mutation-derived spliced peptides

  Grant-in-Aid for Challenging Research (Exploratory)

  Project Year :

  2018.06

  -

  2021.03

   

  Torigoe Toshihiko

  　View Summary

  We could successfully develop the de novo sequencing technology for HLA ligandome analysis, and discovered three spliced peptides derived from wild-type proteins in HCT15 colon cancer cells. Spliced peptide-specific cytotoxic T-cells (CTLs) were induced from peripheral blood lymphocytes of healthy donors by mixed lymphocyte-peptide culture. Two CTL clones were established and analyzed for the cytotoxic potentials, indicating that the novel spliced peptides were highly immunogenic. Then, we analyzed the mechanism of peptide splicing, indicating that the splicing was dependent on the activity of proteasome in the cells. Our data revealed the novel category of neoantigens, which might contribute to the development of a prophylactic cancer vaccine as well as a therapeutic cancer vaccine.

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