Education 【 display / non-display 】

Education 【 display / non-display 】

• 1978

  -

  1984

  National Defense Medical College   Medical Science  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 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

display all >>

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 　

  　

  　

  Cell Stress Society International

• 　

  　

  　

  The Japanese Society of Pathology

• 　

  　

  　

  The Japanese Cancer Association

• 　

  　

  　

  The Japanese Society for Immunology

• 　

  　

  　

  American Association for Cancer Research

display all >>

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 】

• Anti-CTLA-4 Antibody Might Be Effective Against Non-small Cell Lung Cancer With Large Size Tumor.

  Hiroshi Saijo, Yoshihiko Hirohashi, Osamu Honjo, Toyohiro Saikai, Naoki Shijubo, Hirotsugu Takabatake, Akihisa Fujita, Yasuhito Honda, Hiroyuki Koba, Hirofumi Chiba, Toshihiko Torigoe

  Anticancer research   43 ( 9 ) 4155 - 4160  2023.09  [International journal]

  　View Summary

  BACKGROUND/AIM: Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Although several ICI options are available, the treatment regimen for NSCLC with large size tumors (large NSCLC) is controversial and the efficacy of anti-CTLA-4 antibody is unclear. This study thus investigated potential biomarkers for CTLA-4 blockade. PATIENTS AND METHODS: The correlation between tumor diameter and treatment duration was examined in patients with advanced NSCLC treated with anti-PD-1 antibody monotherapy in our institution. In addition, the ratio of tumor-infiltrating CD8+ T cells and regulatory T (Treg) cells in small and large size NSCLC was also evaluated using immunohistochemical staining. Finally, the efficacy of treatment with anti-CTLA-4 antibody against large NSCLC was investigated. RESULTS: A negative correlation was found between tumor diameter and treatment duration in patients treated with anti-PD-1 antibody monotherapy. Immuno-histochemical staining revealed that Treg cell infiltration was significantly higher in large NSCLC tumors than in small tumors. Among the patients with large NSCLC, the ICI regimen including anti-CTLA-4 antibody showed significant efficacies. CONCLUSION: Anti-PD-1 antibody monotherapy might be less effective against large NSCLC due to the infiltration of Treg cells. Therefore, it might be appropriate for large NSCLC to select a treatment including an anti-CTLA-4 antibody, which can target Treg cells.

  DOI PubMed

• ACLP Activates Cancer-Associated Fibroblasts and Inhibits CD8+ T-Cell Infiltration in Oral Squamous Cell Carcinoma.

  Shohei Sekiguchi, Akira Yorozu, Fumika Okazaki, Takeshi Niinuma, Akira Takasawa, Eiichiro Yamamoto, Hiroshi Kitajima, Toshiyuki Kubo, Yui Hatanaka, Koyo Nishiyama, Kazuhiro Ogi, Hironari Dehari, Atsushi Kondo, Makoto Kurose, Kazufumi Obata, Akito Kakiuchi, Masahiro Kai, Yoshihiko Hirohashi, Toshihiko Torigoe, Takashi Kojima, Makoto Osanai, Kenichi Takano, Akihiro Miyazaki, Hiromu Suzuki

  Cancers   15 ( 17 )  2023.08  [International journal]

  　View Summary

  We previously showed that upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in vascular endothelial cells promotes tumor angiogenesis. In the present study, we aimed to clarify the role of stromal AEBP1/ACLP expression in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis showed that ACLP is abundantly expressed in cancer-associated fibroblasts (CAFs) in primary OSCC tissues and that upregulated expression of ACLP is associated with disease progression. Analysis using CAFs obtained from surgically resected OSCCs showed that the expression of AEBP1/ACLP in CAFs is upregulated by co-culture with OSCC cells or treatment with TGF-β1, suggesting cancer-cell-derived TGF-β1 induces AEBP1/ACLP in CAFs. Collagen gel contraction assays showed that ACLP contributes to the activation of CAFs. In addition, CAF-derived ACLP promotes migration, invasion, and in vivo tumor formation by OSCC cells. Notably, tumor stromal ACLP expression correlated positively with collagen expression and correlated inversely with CD8+ T cell infiltration into primary OSCC tumors. Boyden chamber assays suggested that ACLP in CAFs may attenuate CD8+ T cell migration. Our results suggest that stromal ACLP contributes to the development of OSCCs, and that ACLP is a potential therapeutic target.

  DOI PubMed

• Proteogenomic identification of an immunogenic antigen derived from human endogenous retrovirus in renal cell carcinoma.

  Shin Kobayashi, Serina Tokita, Keigo Moniwa, Katsuyuki Kitahara, Hiromichi Iuchi, Kazuhiko Matsuo, Hidehiro Kakizaki, Takayuki Kanaseki, Toshihiko Torigoe

  JCI insight   8 ( 16 )  2023.08  [International journal]

  　View Summary

  CD8+ T cells can recognize tumor antigens displayed by HLA class I molecules and eliminate tumor cells. Despite their low tumor mutation burden, immune checkpoint blockade (ICB) is often beneficial in patients with renal cell carcinoma (RCC). Here, using a proteogenomic approach, we directly and comprehensively explored the HLA class I-presenting peptidome of RCC tissues and demonstrated that the immunopeptidomes contain a small subset of peptides derived from human endogenous retroviruses (hERV). A comparison between tumor and normal kidney tissues revealed tumor-associated hERV antigens, one of which was immunogenic and recognized by host tumor-infiltrating lymphocytes (TIL). Stimulation with the hERV antigen induced reactive CD8+ T cells in healthy donor-derived (HD-derived) peripheral blood mononuclear cells (PBMC). These results highlight the presence of antitumor CD8+ T cell surveillance against hERV3895 antigens, suggesting their clinical applications in patients with RCC.

  DOI PubMed

• Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore.

  Joseph Willis, Robert A Anders, Toshihiko Torigoe, Yoshihiko Hirohashi, Carlo Bifulco, Inti Zlobec, Bernhard Mlecnik, Sandra Demaria, Won-Tak Choi, Pavel Dundr, Fabiana Tatangelo, Annabella Di Mauro, Pamela Baldin, Gabriela Bindea, Florence Marliot, Nacilla Haicheur, Tessa Fredriksen, Amos Kirilovsky, Bénédicte Buttard, Angela Vasaturo, Lucie Lafontaine, Pauline Maby, Carine El Sissy, Assia Hijazi, Amine Majdi, Christine Lagorce, Anne Berger, Marc Van den Eynde, Franck Pagès, Alessandro Lugli, Jérôme Galon

  Cancers   15 ( 16 )  2023.08  [International journal]

  　View Summary

  BACKGROUND: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists' visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. METHODS: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists' T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. RESULTS: Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). CONCLUSIONS: The standardized IS assay outperformed expert pathologists' T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.

  DOI PubMed

• Immunohistological evaluation of patients treated with intra-arterial chemoradiotherapy and surgery for oral cancer.

  Yutaro Ikeuchi, Masanori Someya, Tomokazu Hasegawa, Masato Saito, Shoh Mafune, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Hironari Dehari, Kazuhiro Ogi, Takanori Sasaki, Yoshihiko Hirohashi, Toshihiko Torigoe, Naoki Hirokawa, Akihiro Miyazaki, Koh-Ichi Sakata

  Medical molecular morphology    2023.07  [Domestic journal]

  　View Summary

  Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000-2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (P = 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (P = 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (P = 0.009 and P = 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer.

  DOI PubMed

display all >>

Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Advances of cancer immunotherapy: pan-cancer rationale and perspectives

  鳥越俊彦

  札幌冬季がんセミナー   37th  2023

  J-GLOBAL

• Analysis of immunopathological phenotype of ERposi. breast ca. by multiplex immunohistochemistry

  淺沼広子, 廣橋良彦, 九冨五郎, 島宏明, 鳥越俊彦

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

• Analysis of ED-SCLC by Subtype Treated with ICIs and Chemotherapy Combination as First-Line Therapy

  四十坊直貴, 四十坊直貴, 久保輝文, 佐々木健太, 廣橋良彦, 鳥越俊彦

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

• Comprehensive single-cell immune profiling of tumor-infiltrating lymphocytes in acral melanoma

  箕輪智幸, 箕輪智幸, 村田憲治, 廣橋良彦, 宇原久, 鳥越俊彦

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

• Analysis of tumor microenvironment based on histology

  廣橋良彦, 久保輝文, 金関貴幸, 塚原智英, 鳥越俊彦

  日本病理学会会誌   112 ( 1 )  2023

  J-GLOBAL

display all >>

Awards 【 display / non-display 】

Awards 【 display / non-display 】

• Hokkaido Scientific Technology Prize

  2023.02   Hokkaido Prefecture  

• The Akiyama Foundation Prize

  2022.09   The Akiyama Life Science Foundation  

• 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

display all >>

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

   

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

  Grant-in-Aid for Challenging Research (Pioneering)

  Project Year :

  2021.07

  -

  2025.03

   

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

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

  -

  2023.03

   

• 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.

• Novel vaccination targeting stem cells of cervical cancer

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2017.04

  -

  2021.03

   

  Saito Tsuyoshi

  　View Summary

  Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small subpopulation of cancer cells that are tumorigenic and are resistant to treatments, thus they are focused as treatment targets. We have established sphere-cultured CSCs/CICs from primary human uterine cervical carcinoma, and we isolated several clones from CSCs/CICs in this study. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6-overexpressing cervical cancer cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy.

display all >>