Specialty
Tumor Immunology, Viral Immunology & Transplantation Immunology
Research team - A Research Team Dedicated to Translational Immunology in The University of Hong Kong
weblink: https://paed.hku.hk/menu/staff/wwtu/index.html

My long-standing research interest is to discover and translate the novel discoveries in the field of immunology to the delivery of effective immunological solutions for relevant human diseases.

Tumor Immunology: To understand the mechanisms underlying the interactions between immune cells and tumor cells and develop novel antitumor approaches, i.e. γδ-T cells-based antitumor immunotherapy. Previously we showed that a novel strategy by targeting γδ-T cells with phosphoantigen can control EBV-induced B cell lymphoma (Cancer Cell 2014). Recently we further found that γδ-T cells-derived exosomes can control EBV-associated tumors by killing tumor cells and enhancing T cells-mediated antitumor immune responses (Sci Transl Med 2020). More recently we have developed a γδ-T cells exosomes-based tumor vaccine to prevent and treat cancers (J Extracell Vesicles 2023). Now we are focusing on translation of the newly developed γδ-T cells-based cancer therapies from bench to bedside.

Viral Immunology: To understand cellular and molecular basis involved in the host immune responses to influenza viruses and develop novel antiviral strategies. We discovered a novel mechanism of influenza virus to evade NK cell immunity (J Virol 2009; J Virol 2010). We also developed a novel strategy to treat human and avian influenza diseases by using an old drug pamidronate to enhance γδ-T cell immunity (J Infect Dis 2009; J Virol 2011; J Exp Med 2011; J Infect Dis 2012; Cell Mol Immunol 2013c, 2017; Front Immunol 2017, 2018; Signal Transduct Target Ther 2020). Now we are studying the immune surveillance to influenza virus and SARS-CoV-2.

Transplantation Immunology: To understand the basic processes that control T-cell-mediated inflammation and tolerance. We have developed the novel methods to generate antigen-specific CD4 and CD8 regulatory T cells (Tregs) (Blood 2008; J Immunol 2009; Cell Mol Immunol 2010; Eur J Immunol 2011; Plos One 2013a; Plos One 2013b). We also confirmed that ex vivo-generated human CD8 Tregs can control graft-versus-host disease (GVHD) in an allospecific manner while leaving graft versus tumor and general immune responses intact in humanized mice (Sci Transl Med 2013). We are now focusing on translating these basic studies into the development of new therapies for GVHD, organ transplantation and autoimmune diseases.

Humanized Mouse Model: We have established the humanized mice with complete human immune system previously (J Exp Med 2011). Using humanized mice, we have successfully established different disease models, such as tumors, virus infection, graft-versus-host disease (GVHD) and allograft transplantation models (J Exp Med 2011; Cancer Cell 2014; Sci Transl Med 2013, 2020). Now we are focusing on establishment of patient-derived xenografts (PDX) and different autoimmune disease models in humanized mice.

1. Wang X#, Zhang Y, Chung Y, Tu CR, Zhang W, Mu X, Wang M, Chan GCF, Leung WH, Lau YL, Liu Y and Tu W*. Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities. Journal of Extracellular Vesicles. 2023 Sep;12(9):e12360. doi: 10.1002/jev2.12360.
2. Cai S, Dai S, Lin R, Huang C, Zeng Y, Diao L, Lian R, Tu W*. The effectiveness and safety of intrauterine infusion of autologous regulatory T cells (Tregs) in patients with recurrent pregnancy loss and low levels of endometrial FoxP3+ cells: A retrospective cohort study. American Journal of Reproductive Immunology. 2023 Aug; 90(2): e13735. https://doi.org/10.1111/aji.13735.
3. Mu X, Cohen CA, Leung D, Duque JSR, Cheng SMS, Cheng SSM, Chung Y, Wong HHW, Lee AMT, Li WY, Tam IYS, Lam JHY, Lee DHL, Chan SM, Tsang LCH, Chan KCK, Li JKC, Luck LLH, Chaothai S, Kwan KKH, Chu NC, Mori M, Jeevan T, Kandeli A, Webby RJ, Tu W*, Valkenburg S*, Peiris M* and Lau YL* Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after the third dose of BNT162b2 in healthy adolescents. Signal Transduction and Targeted Therapy. 2022; 7:397. Dec 14 2022. Doi: 10.1038/s41392-022-01282-7
4. Tsang TK, Lam KT, Liu Y, Fang VJ, Leung NHL, Peiris JSM, Leung GM, Cowling B*, Tu W* Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study. BMC Medicine. 2022, July 21. 20, 230. https://doi.org/10.1186/s12916-022-02429-7.
5. Mu, X, Xiang Z, Yan Xu Y, He J, Lu J, Chen Y, Wang X, Tu CR, Zhang YM, Yin Z, Leung WH, Lau YL, Liu Y, Tu W*. Glucose metabolism controls human γδ-T cell-mediated tumor immunosurveillance in diabetes. Cellular and Molecular Immunology. July 11, 2022. https://doi.org/10.1038/s41423-022-00894-x
6. Duque JSR#, Wang X#, Leung D#, Cheng SMS#, Cohen CA#, Mu X, Hachim A, Zhang Y, Chan SM, Chaothai S, Kwan KKH, Chan KCK, Li JKC, Luk LLH, Tsang LCH, Wong WHS, Cheang CH, Hung TK, Lam JHY, Chua GT, Tso WWY, Ip P, Kavian N, Leung WH, Valkenburg S, Peiris M*, Tu W* and Lau YL*. Immunogenicity and reactogenicity of SARS-CoV-2 mRNA and inactivated vaccines in healthy adolescents. Nature Communications. June 28. 2022; 13:3700 | https://doi.org/10.1038/s41467-022-31485-z.
7. Wang X#, Zhang Y#, Mu X, Tu CR, Chung Y, Tsao SW, Chan GCF, Leung WH, Lau YL, Liu Y and Tu W*. Exosomes derived from γδ-T cells synergize with radiotherapy and preserve antitumor activities against nasopharyngeal carcinoma in immunosuppressive microenvironment. Journal for Immunotherapy of Cancer 2022;0:e003832. doi:10.1136/jitc-2021-003832.
8. Wang X, Xiang Z, Liu Y, Huang C, Pei Y, Wang X, Zhi H, Wong WH, Wei H, Ng IO, Lee PP, Chan GC, Lau YL, Tu W*. Exosomes derived from Vδ2+-T cells control Epstein-Barr virus-associated tumors and induce T-cell antitumor immunity. Science Translational Medicine. 2020 Sep 30;12(563):eaaz3426. doi: 10.1126/scitranslmed.aaz3426.
9. Pei Y, Wen K, Xiang Z, Huang C, Wang X, Mu X, Wen L, Liu Y, Tu W*. CD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus. Signal Transduction and Targeted Therapy. 2020 Jun 3;5(1):74. doi: 10.1038/s41392-020-0174-2.
10. Wang X, Xiang Z, Tsao GS, Tu W*. Exosomes derived from nasopharyngeal carcinoma cells induce IL-6 production from macrophages to promote tumorigenesis. Cellular and Molecular Immunology. 2020 Apr 1. doi: 10.1038/s41423-020-0420-0.
11. Tu W* and Zheng J. Chapter 10. Application of Humanized Mice in Immunological Research. In: Maria Cristina Cuturi and Ignacio Anegon (eds.), Suppression and Regulation of Immune Responses: Methods and Protocols, Volume II, Methods in Molecular Biology, vol. 1371, DOI 10.1007/978-1-4939-3139-2_10, © Springer Science+Business Media New York 2016
12. Chen Q, Wen K, Lv A, Liu M, Ni K, Xiang Z, Liu Y, Tu W*. Human Vγ9Vδ2-T cells synergize CD4+ Tfh cells to produce influenza virus-specific antibody. Frontiers in Immunology, 04 April 2018 | https://doi.org/10.3389/fimmu.2018.00599.
13. Xiang Z and Tu W*. Dual face of Vγ9Vδ2-T cells in tumor immunology: anti- versus pro-tumoral activities. Frontiers in Immunology, 2017 Aug 28;8:1041. doi: 10.3389/fimmu.2017.01041. eCollection 2017.
14. Liu Y, Zheng J, Liu Y, Wen L, Huang L, Xiang Z, Lam KT, Lv A, Mao H, Lau YL, Tu W*. Uncompromised NK cell activation is essential for virus-specific CTL activity during acute influenza virus infection. Cellular and Molecular Immunology. 2017 Apr 17. doi: 10.1038/cmi.2017.10.
15. Chen Q, Liu Y, Lu A, Ni K, Xiang Z, Wen K, Tu W*. Influenza virus infection exacerbates experimental autoimmune encephalomyelitis disease by promoting type I T cells infiltration into central nervous system. J Autoimmun. 2017 Feb;77:1-10. doi: 10.1016/j.jaut.2016.10.006.
16. Wu Y, Tu W*, Lam KT, Chow KH, Ho PL, Guan Y, Peiris JS, Lau YL. Lethal co-infection of influenza virus and Streptococcus pneumoniae lowers antibody response to influenza virus in lung, and reduces germinal center B cells, T follicular helper cells and plasma cells in mediastinal lymph node. Journal of Virology. 2015 Feb;89(4):2013-23. doi: 10.1128/JVI.02455-14.
17. Xiang Z, Liu Y, Zheng J, Liu M, Lv A, Gao Y, Hu H, Lam KT, Chan GC, Yang Y, Chen H, Tsao GS, Bonneville M, Lau YL, Tu W*. Targeted activation of human Vg9Vd2-T cells controls Epstein-Barr virus-induced B cell lymphoproliferative disease. Cancer Cell 2014 Oct 13;26(4):565-576. doi: 10.1016/j.ccr.2014.07.026.
18. Li J, Li H, Mo H, Yu M, Feng T, Yang F, Fan Y, Lu Q, Shen C, Yin Z, Mao M, Tu W*. Impaired NK cell antiviral cytokine response against influenza virus in small-for-gestational-age neonates. Cellular and Molecular Immunology 2013 Sep;10(5):437-43. doi: 10.1038/cmi.2013.31.
19. Zheng J, Liu Y, Liu M, Xiang Z, Lam KT, Lewis DB, Lau YL, Tu W*. Human CD8 regulatory T cells inhibit graft-versus-host disease and preserve general immunity in humanized mice. Science Translational Medicine 2013 Jan 16;5(168):168ra9.
20. Zheng J, Liu Y, Lau YL and Tu W*. Gammadelta-T Cells: unpolished sword in human antiviral Immunity. Cellular and Molecular Immunology, 2013 Jan;10(1):50-7.
21. Qin G, Liu Y, Zheng J, Ng IH, Peiris JSM, Lau YL and Tu W*. Phenotypic and functional characterization of human γδ T cell subsets in response to influenza A viruses. Journal of Infectious Diseases. 2012 Jun;205(11):1646-53.
22. Mao H, Yang W, Lee PPW, Ho MHK, Yang J, Zeng S, Chong CY, Lee TL, Tu W*, Lau YL. Exome Sequencing Identifies Novel Compound Heterozygous Mutations in Interleukin-10 Receptor A in a Neonatal-Onset Crohn’s Disease Patient. Genes and Immunity 2012 Jul;13(5):437-42.
23. Qin G, Liu Y, Zheng J, Ng IH, Xiang Z, Lam KT, Mao H, Li H, Peiris JSM, Lau YL and Tu W*. Type-1 responses of human Vγ9Vδ2 T cells to influenza A viruses. Journal of Virology. 2011 oct; 85(19):10109-16
24. Tu W*, Zheng J, Liu Y, Sia SF, Liu M, Qin G, Ng IHY, Lam KT, Peiris JSM, and Lau YL. The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a gammadelta T cell population in humanized mice. Journal of Experimental Medicine. 2011 Jul 4; 208(7):1511-22.
25. Tu W*, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L, Guan Y, Yuen KY, Peiris JSM and Lau YL. Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus. Journal of Virology. 2010 Jul;84(13):6527-35.
26. Mao H, Tu W*, Qin G, Law HKW, Sia SF, Chan PL, Liu Y, Lam KT, Zheng J, Peiris JSM and Lau YL. Influenza virus directly infects human natural killer cells and induces cell apoptosis. Journal of Virology. 2009 Sep;83(18):9215-22.
27. Zheng J, Liu Y, Qin G, Chan PL, Mao H, Lewis DB, Lau YL and Tu W*. Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells. Journal of Immunology 2009 Sep 15;183(6):3742-50.
28. Qin G, Mao H, Zheng J, Sia FS, Liu Y, Peiris JSM, Lau YL and Tu W*. Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages. Journal of Infectious Diseases 2009 Sep 15;200(6):858-65.
29. Tu W*, Lau YL, Zheng J, Liu Y, Chan PL, Mao H, Dionis K, Schneider P, and Lewis DB. Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naïve precursors by CD40-activated B cells. Blood. 2008:112(6):2554-62.
30. Tu W, Potena L, Stepick-Biek P, Liu L, Dionis KY, Luikart H, Fearon WF, Holmes TH, Chin C, Cooke JP, Valantine HA, Mocarski ES, Lewis DB. T-Cell Immunity to Subclinical Cytomegalovirus Infection Reduces Cardiac Allograft Disease. Circulation. 2006 Oct; 114(15): 1608-15.

Research Grants (External)

1. The effect of saturated and unsaturated fatty acids on the antitumor activity of human γδ-T cells (GRF - 2024) PI.
2. Targeting m6A modification to boost chemotherapy and immunotherapy efficacy in colorectal cancer (CRF - 2024) Co-PI.
3. Preclinical development of chimeric antigen receptor engineered NK-cells for acute myeloid leukaemia (GRF - 2024) PI.
4. Development of gammadelta-T cell exosomes-based therapeutic cancer vaccines against Epstein-Barr virus-associated tumors (GRF - 2023) PI.
5. Development of chimeric antigen receptor engineered T-cell therapy for T-lineage malignancy (GRF - 2023) PI.
6. Effect of glucose metabolism on tumor immunosurveillance of human Vγ9Vδ2-T cells. (GRF - 2022) PI.
7. Therapeutic effect of human γδ-T-cell-derived-exosomes on nasopharyngeal carcinoma in preclinical models (HMRF - 2021) PI.
8. Analysis of anti-tumor activity of human γδ T cells in humanized mice (Germany/Hong Kong Joint Research Scheme 2020/21) PI.
9. Roles of exosomes-induced IL-17-producing γδ-T cells in the development and progression of nasopharyngeal carcinoma (GRF - 2019) PI.
10. Costimulatory effect of 4-1BB signal in the antitumor activity of human gammadelta-T cells against EBV-induced lymphoproliferative disease (GRF - 2017) PI.
11. Role of costimulatory molecule CD137 in the antiviral activity of human gammadelta-T cells against influenza virus (GRF - 2015) PI.
12. Viral, host and environmental determinants of influenza virus transmission and pathogenesis. [Theme-based Research Scheme (TRS) - 2014] Co-PI.
13. Center for Nasopharyngeal Carcinoma Research, 2nd phase. [Areas of Excellence (AoE), - 2014] CI.
14. Human gammadelta-T cell-mediated virus-specific immune regulation during influenza virus infection (GRF - 2014) PI.
15. Role of human gammadelta-T cells in the generation of influenza virus-specific antibody (GRF - 2013) PI.
16. Antiviral activity of human gammadelta-T cells against Enterovirus 71. (HMRF - 2013)/PI.
17. Induction of tolerance by alloantigen-specific regulatory T cells in humanized mice and non-human primates. (NSFC/RGC Joint Research Scheme - 2011)/PI.
18. Antiviral Activity of Human gammadelta-T Cells against Epstein-Barr Virus Infection. (GRF - 2011)/ PI.
19. Immune Evasion of Natural Killer Cells by Influenza Virus in Vivo (Research Fund for the Control of Infectious Diseases - 2011)/ PI.
20. Rotavirus Vaccine Programme (Hong Kong Society for the Relief of Disabled Children - 2009) Co-PI.
21. Pneumococcal Vaccine Programme. (Hong Kong Society for the Relief of Disabled Children - 2009) Co-PI.
22. The Role of Natural Killer Cells in the Pathogenesis of Avian Influenza Virus Infection. (GRF - 2008) PI.
23. Control of Pandemic and Inter-Pandemic Influenza. [Areas of Excellence (AoE) – 2008] CI.
24. Immune defense of human gammadelta-T Cells against influenza A viruses. (GRF - 2007) PI.
25. Humanized mouse as a model to study the antiviral activity of human gammadelta-T cells against human and avian influenza A viruses in vivo. (Research Fund for the Control of Infectious Diseases - 2007) PI.

Patents (granted)

1. Method to induce and expand therapeutic alloantigen-specific human regulatory T cells in large-scale (USPT patent: US8658159B2)
2. Method to induce and expand therapeutic alloantigen-specific human regulatory T cells in large-scale (European Patent: 2300602)
3. 大规模诱导和扩增治疗性同种异体抗原特异性的人调节性Ｔ细胞的方法。（China patent: 200980125228.0）
4. Patent Cooperation Treaty: Methods to generation of human alloantigen-specific CD4 regulatory T cells. (PCT/CN2009/000484).
5. Human CD8 regulatory T cells inhibit graft-versus-host disease and preserve general immunity (USPT patent: US10,092,597 B2, Oct 9, 2018).
6. Biophosphonate Compounds and Gamma Delta T Cell-Mediated Therapy for Treating Epstein-Barr Virus Associated Disorders (PTC/CN2015/086745)
7. Biophosphonate Compounds and Gamma Delta T Cell-Mediated Therapy for Treating Epstein-Barr Virus Associated Disorders (USPT patent: 10532064 B2; 2020).
8. 治疗EBV相关疾病的双磷酸盐化合物和γδT细胞介导的疗法 (China patent: 201580055215.6)
9. 制备V-T 细胞衍生的外泌体以治疗EPSTEIN-BARR 病毒相关癌症的方法 (China patent: 202080072732.5).

• 2015:  Outstanding Research Output Award, LKS Faculty of Medicine, HKU.
• 2004:  The second class prize of “The Progress of Science and Technology” was awarded by the Ministry of Education of the People’s Republic of China for the study on “Neonatal Immune Functions”.
• 2002:  Travel award for Federation of Clinical Immunology Societies, USA
• 2002:  The second class prize of “The Progress of Science and Technology” was awarded by Chongqing Municipal Government for the study on “Developmental Immune Dysfunctions”.
• 2001:  Dean Fellowship, Stanford University
• 2000:  Dean Fellowship, Stanford University
• 1998:  The third class prize of “The Progress of Science and Technology” was awarded by Chongqing Municipal Government for the study on “The immunoregulatory role of Chinese herb Astragalus membranaceus and its clinical significance”.
• 1997:  The first class prize of“The Progress of Science and Technology” was awarded by Chongqing Municipal Government for the study on “T lymphocyte dysfunction and clinical diseases”.
• 1994:  The second class prize of “The Progress of Science and Technology” was awarded by Sichuan Province Government for the study on “The role of T cells and their cytokines in immunoglobulin isotype switching and their clinical significance”.

Editorship or editorial board membership of scholarly journals

	2015-:	Guest editor for PLOS Pathogens.
	2015-:	Member of Editorial Board, Frontiers in Immunology
	2013-:	Member of Editorial Board. Virologica Sinica.
	2012-:	Member of Editorial Board. Dataset Papers in Medicine (Hindawi Publish Corporation).
	2012:	Member of Editorial Board. Scientifica (Hindawi Publish Corporation).
	2010-:	Member of Editorial Board. Cellular and Molecular Immunology (Nature Publishing Group)
	2008-:	Member of Editorial Board. Journal of Pediatric Pharmacology.
	2007-:	Member of Editorial Board. Chinese Journal of Paediatrics

Leadership in Professional Society

	Council member	Chinese NSFC Board of Medical Research (2018)
	Chair	Symposium at Primary and acquired Immunodeficiency 2016 World Life Science Congress, Beijing (2016)
	Members	Expert group responsible for drafting the chapters of the Immunology Research and Development for Chinese NSFC 13th-5 Years Strategy Plan (2014).
	President	Hong Kong Society of Immunology (2012-2014).
	President	Hong Kong Society of Flow Cytometry (2010-2011)
	Council member	Paediatric Infectious Disease Committee, Chinese Medical Association. (2010- )
	Member	Evaluation Committee for Chang Jiang Scholars, Ministry of Education of the People’s Republic of China, China (2009- )
	Chair	Viral Infection Symposium at 13th Asian Pacific Congress of Pediatrics (2009)
	Council member	Chinese National Pediatric Virology Group (2008- )
	Council member	Hong Kong Society of Immunology (2008- )
	Council member	Paediatric Immunology Committee, Chinese Medical Association (2007-2010)

Teaching 

6 MPhil students (5 graduated), 10 PhD students (7 graduated)