Naoto Hirano

Dr. Hirano's research program aims to devise novel anti-tumor immunotherapeutic modalities that can cure cancer. Dr. Hirano’s research team is particularly interested in understanding how the interactions between T cells and antigen-presenting cells affect priming, expansion, persistence and differentiation of T cells, as well as how this leads to the subsequent generation and maintenance of anti-tumor T cell memory.

Find out more about Dr. Hirano's research focus.

Recent Publications

1. Murata K, Ly D, Saijo H, Matsunaga Y, Sugata K, Ihara F, Oryoji D, Ohashi Y, Saso K, Wang C-H, Zheng EYF, Burt B, Butler MO, Hirano N. Modification of the HLA-A*24:02 peptide binding pocket enhances cognate peptide-binding capacity and antigen-specific T cell activation. J Immunol. 2022.
    
2. Boukhaled GM, Gadalla R, Elsaesser HJ, Abd-Rabbo D, Quevedo R, Yang SYC, Guo M, Wang BX, Noamani B, Gray D, Lau SCM, Taylor K, Aung K, Spreafico A, Hansen AR, Saibil SD, Hirano N, Guidos C, Pugh TJ, McGaha TL, Ohashi PS, Sacher AG, Butler MO, Brooks DG. Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy. Nat Immunol. 2022.
    
3. Kato K, Nakatsugawa M, Tokita S, Hirohashi Y, Kubo T, Tsukahara T, Murata M, Chiba H, Takahashi H, Hirano N, Kanaseki T, Torigoe T. Characterization of proteasome-generated spliced peptides detected by mass spectrometry. J Immunol. 2022.
    
4. Kanwar N, Balde Z, Nair R, Dawe M, Chen S, Maganti M, Atenafu EG, Manolescu S, Wei C, Mao A, Fu F, Wang D, Cheung A, Yerofeyeva Y, Peters R, Liu K, Desmedt C, Sotiriou C, Szekely B, Kulka J, McKee TD, Hirano N, Bartlett JMS, Yaffe MJ, Bedard PL, McCready D, Done SJ. Heterogeneity of Circulating Tumor Cell-Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response. Cancer Res. 2021.
    
5. Sugata K, Matsunaga Y, Yamashita Y, Nakatsugawa M, Guo T, Halabelian L, Saso K, Rahman MA, Anczurowski M, Wang C-H, Murata K, Saijo H, Kagoya Y, Ohashi Y, Burt BD, Ly D, Butler MO, Mak TW, Hirano N. Affinity-matured HLA class II dimers for robust staining of antigen-specific CD4⁺ T cells. Nat Biotechnol. 2021.
    
6. Rahman MA, Murata K, Burt BD, Hirano N. Changing the landscape of tumor immunology: Novel tools to examine T cell specificity. Current Opin Immunol. 2021.
    
7. Murata K, Nakatsugawa M, Rahman MA, Nguyen LT, Millar DG, Mulder DT, Sugata K, Saijo H, Matsunaga Y, Kagoya Y, Guo T, Anczurowski M, Wang C-H, Burt BD, Ly D, Saso K, Easson A, Goldstein DP, Reedijk M, Ghazarian DA, Pugh TJ, Butler MO, Mak TW, Ohashi PS, Hirano N. Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma. eLife. 2020.
    
8. Kagoya Y, Guo T, Yeung B, Saso K, Anczurowski M, Wang C-H, Murata K, Sugata K, Saijo H, Matsunaga Y, Ohashi Y, Butler MO, Hirano N. Genetic ablation of HLA class I, class II, and the T cell receptor enables allogeneic T cells to be used for adoptive T cell therapy. Cancer Immunol Res. 2020.
    
9. Ochi T, Maruta M, Hirano N. Modification and immunological analyses for the development of immunotherapy utilizing T cells redirected with antigen-specific receptors. Methods Mol Biol. 2019.
    
10. Anczurowski M, Sugata K, Matsunaga Y, Yamashita Y, Wang C-H, Guo T, Murata K, Saijo H, Kagoya Y, Saso Y, Butler MO, Hirano N. Chaperones of the class I peptide-loading complex facilitate the constitutive presentation of endogenous antigens on HLA-DP^84GGPM87. J Autoimmun. 2019.
     
11. Gadalla R, Naomani B, MacLeod B, Dickson R, Guo M, Xu W, Lukhele S, Elsaesser HJ, Razak A, Hirano N, McGaha TL, Wang B, Butler MO, Guidos CJ, Ohashi PS, Siu L, Brooks DG. Validation of CyTOF against flow cytometry for immunological studies and monitoring of human cancer clinical trials. Front Oncol. 2019.
     
12. Nguyen LT, Saibil SD, Sotov V, Le MX, Khoja L, Ghazarian D, Bonilla L, Majeed H, Hogg D, Joshua A, Crump M, Franke N, Spreafico A, Hansen A, Al-Habeeb A, Leong W, Easson A, Reedijk M, Goldstein D, McCready D, Yasufuku K, Waddell T, Cypel M, Pierre A, Zhang B, Boross-Harmer S, Cipollone J, Nelles M, Scheid E, Fyrsta M, Lo C, Nie J, Yam J, Yen P-H, Gray D, Motta V, DeLuca S, Wang L, Effendi S, Ellenchery R, Hirano N, Ohashi PS, and Butler MO. Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma using autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. Cancer Immunol Immunother. 2019.
     
13. Benveniste PM, Nakatsugawa M, Nguyen L, Ohashi PS, *Hirano N, *Zúñiga-Pflücker JC (*These two authors contributed equally). In vitro-generated MART-1-specific CD8 T cells display a broader T cell receptor repertoire than naïve ex vivo and tumor infiltrating lymphocytes. Immunol Cell Biol. 2019
     
14. Kagoya Y, Saijo H, Matsunaga Y, Guo T, Saso K, Anczurowski M, Wang C-H, Sugata K, Murata K, Butler MO, Arrowsmith CH, Hirano N. Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells. J Autoimmun. 2019
     
15. Benveniste PM, Roy S, Nakatsugawa M, Chen ELY, Nguyen L, Millar DG. Ohashi PS, Hirano N, Adams EJ, Zúñiga-Pflücker JC. Generation and molecular recognition of melanoma-associated antigen-specific human γδ T cells. Sci Immunol. 2018
     
16. Anczurowski M, Hirano N. Mechanisms of HLA-DP antigen processing and presentation revisited. Trends Immunol. 2018
     
17. Mulder DT, Mahé ER, Dowar M, Hanna Y, Li T, Nguyen L, Butler MO, Hirano N, Delabie J, Ohashi P, Pugh TJ. CapTCR-seq: A hybrid capture method for assessment of T-cell receptor clonality. Blood Adv. 2018
     
18. Anczurowski M, Hirano N. Two weeks' notice from allogeneic sources. Clin Cancer Res. 2018
     
19. Kagoya Y, Nakatsugawa M, Guo T, Ochi T, Saso K, Anczurowski M, Butler MO, Arrowsmith CH, Hirano N. DOT1L inhibition enables the safe and effective use of allogeneic antitumor T cells in adoptive immunotherapy models. Nat Commun. 2018
     
20. Achita P, Dervović D, Ly D, Lee JB, Haug T, Joe B, Hirano N, Zhang Li. Infusion of ex vivo expanded human TCRαβ+ double negative regulatory T cells delays onset of xenogeneic graft-versus-host disease. Clin Exp Immunol. 2018
     
21. Anczurowski M, Yamashita Y, Nakatsugawa M, Ochi T, Kagoya Y, Guo T, Wang C-H, Rahman MA, Saso K, Butler MO, Hirano N. Mechanisms underlying the lack of endogenous processing and CLIP-mediated binding of the invariant chain by HLA-DP^84Gly. Sci Rep. 2018
     
22. Kagoya Y, Tanaka S, Guo T, Anczurowski M, Wang C-H, Saso K, Butler MO, Minden MD, Hirano N. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nat Med. 2018
     
23. Guo T, Koo MY, Kagoya Y, Anczurowski M, Wang C-H, Saso K, Butler MO, Hirano N. A subset of human autoreactive CD1c-restricted T cells preferentially express TRBV4-1⁺ TCRs. J Immunol. 2018
     
24. Rozanov DV, Rozanov ND, Chiotti K, Reddy A, Wilmarth PA, David LL, Cha SW, Woo S, Pevzner P, Bafna V, Burrows GG, Rantala JK, Levin T, Anur P, Johnson-Canacho K, Tabatabaei S, Munson DJ, Bruno TC, Slansky JE, Kappler JW, Hirano N, Boegel S, Fox BA, Egelston C, Simons DL, Jimenez G, Lee PP, Gray JW, Spellman PT. MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection. J Proteomics. 2018
     
25. Yamashita Y, Anczurowski M, Nakatsugawa M, Tanaka M, Kagoya Y, Sinha A, Chamoto K, Ochi T, Guo T, Saso K, Butler MO, Minden M, Kislinger T, Hirano N. HLA-DP^84Gly constitutively presents endogenous peptides generated by the class I antigen processing pathway. Nat Commun. 2017
     
26. Ghazarian M, Revelo XS, Zeng K, Luck H, Lei H, Tsai S, Chng MHY, Shen L, D’Angelo JA, Horton P, Chapman WC, Brockmeier D, Engleman EG, Adeyi O, Hirano N, Jin T, Gehring AJ, Winer S, Winer D. Type I interferon responses drive intrahepatic T cells to promote metabolic syndrome. Sci Immunol. 2017
     
27. Chamoto K, Guo T, Scally SW, Kagoya Y, Anczurowski M, Wang C-H, Rahman MA, Saso K, Butler MO, Chiu PPL, Julien JP, Hirano N. Key residues at third CDR3β position impact function and structure of human invariant NKT-cell receptors. J Immunol. 2017
     
28. Kagoya Y, Nakatsugawa M, Ochi T, Guo T, Cen Y, Saso K, Butler MO, Hirano N. Transient but not prolonged stimulation expands superior antitumor T cells for adoptive therapy. JCI Insight. 2017
     
29. Merkel PA, Xie G, Monach PA, Ji X, Ciavatta DJ, Byun J, Pinder BD, Zhao Z, Zhang J, Tadesse Y, Qian D, Weirauch M, Nair R, Tsoi A, Ripke S, Pagnoux C, Carette S, Chung S, Cuthbertson D, Davis JC, Jr., Dellaripa PF, Forbess L, Gewurz-Singer O, Hoffman GS, Khalidi N, Koening C, Langford CA, Mahr AD, McAlear C, Moreland L, Seo EP, Specks U, Spiera RF, Sreih A, William St. Clair E, Stone JH, Ytterberg SR, Elder JT, Qu J, Ochi T, Hirano N, Edberg JC, Falk RJ, Amos CI, and Siminovitch KA for the Vasculitis Clinical Research Consortium. Identification of functional and expression polymorphisms associated with risk for anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Arthritis Rheumatol. 2017
     
30. Kagoya Y, Nakatsugawa M, Yamashita Y, Ochi T, Guo T, Anczurowski M, Saso K, Butler MO, Arrowsmith CH, Hirano N. BET bromodomain inhibition generates superior antitumor CD8⁺ T cells with features of stem cell-like and central memory T cells for adoptive immunotherapy. J Clin Invest. 2016
     
31. Guo T, Ochi T, Nakatsugawa M, Kagoya Y, Anczurowski M, Wang C-H, Rahman MA, Saso K, Butler MO, Hirano N. Generating de novo antigen-specific human T cell receptors by retroviral transduction of centric hemichain. J Vis Exp. 2016
     
32. Chamoto K, Guo T, Imataki O, Tanaka M, Nakatsugawa M, Ochi T, Yamashita Y, Saito AM, Saito TI, Butler MO, Hirano N. CDR3β sequence motifs regulate autoreactivity of human invariant NKT cell receptors. J Autoimmun. 2016
     
33. Nakatsugawa M, Rahman MA, Yamashita Y, Ochi T, Wnuk P, Tanaka S, Chamoto K, Kagoya Y, Saso K, Guo T, Anczurowski M, Butler MO, Hirano N. CD4⁺ and CD8⁺ TCRβ repertoires possess different potentials to generate extraordinarily high-avidity T cells. Sci Rep. 2016
     
34. Guo T, Chamoto K, Nakatsugawa M, Ochi T, Yamashita Y, Anczurowski M, Butler MO, Hirano N. Mouse and Human CD1d-Self-Lipid Complexes Are Recognized Differently by Murine Invariant Natural Killer T Cell Receptors. PLoS One. 2016
     
35. Ochi T, Nakatsugawa M, Chamoto K, Tanaka S, Yamashita Y, Guo T, Fujiwara H, Yasukawa M, Butler MO, Hirano N. Optimization of T-cell reactivity by exploiting TCR chain centricity for the purpose of safe and effective antitumor TCR Gene Therapy. Cancer Immunol Res. 2015
     
36. Nakatsugawa M, Yamashita Y, Ochi T, Tanaka S, Chamoto K, Guo T, Butler MO, Hirano N. Specific roles of each TCR hemichain in generating functional chain-centric TCR. J Immunol. 2015
     
37. Guo T, Chamoto K, Hirano N. Adoptive T Cell Therapy Targeting CD1 and MR1. Front Immunol. 2015
     
38. Butler MO, Hirano N. Human cell-based artificial antigen-presenting cells for cancer immunotherapy. Immunol Rev. 2014
     
39. Imataki O, Ansén S, Tanaka M, Butler MO, Berezovskaya A, Milstein MI, Kuzushima K, Nadler LM, Hirano N. IL-21 can supplement suboptimal Lck-independent MAPK activation in a STAT-3-dependent manner in human CD8⁺ T cells. J Immunol. 2012
     
40. Butler MO, Imataki O, Yamashita Y, Tanaka M, Ansén S, Berezovskaya A, Metzler G, Milstein MI, Mooney MM, Murray AP, Mano H, Nadler LM, Hirano N. Ex vivo expansion of human CD8⁺ T cells using autologous CD4⁺ T cell help. PLoS One. 2012
     
41. Butler MO, Friedlander P, Milstein MI, Mooney MM, Metzler G, Murray AP, Tanaka M, Berezovskaya A, Imataki O, Drury L, Brennan L, Flavin M, Neuberg D, Stevenson K, Lawrence D, Hodi FS, Velazquez EF, Jaklitsch MT, Russell SE, Mihm M, Nadler LM, Hirano N. Establishment of antitumor memory in humans using in vitro-educated CD8⁺ T cells. Sci Transl Med. 2011
     
42. Tanaka M, Butler MO, Ansén S, Imataki O, Berezovskaya A, Nadler LM, Hirano N. Induction of HLA-DP4-restricted anti-survivin Th1 and Th2 responses using an artificial antigen-presenting cell. Clin Cancer Res. 2011

Appointments

Associate Director for Research, Tumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network