International Journal of Stem Cells

  • 제16권1호
  • /
  • Pages.108-116
  • /
  • 2023
  • /
  • 2005-3606(pISSN)
  • /
  • 2005-5447(eISSN)
한국줄기세포학회 (Korean Society for Stem Cell Research)
권호 표지
DOI QR코드

DOI QR Code

Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

  • Soo-Been Jeon (CHA Advanced Research Institute, CHA Bundang Medical Center, CHA University) ;
  • A-Reum Han (CHA Advanced Research Institute, CHA Bundang Medical Center, CHA University) ;
  • Yoo Bin Choi (CHA Advanced Research Institute, CHA Bundang Medical Center, CHA University) ;
  • Ah Reum Lee (CHA Advanced Research Institute, CHA Bundang Medical Center, CHA University) ;
  • Ji Yoon Lee (CHA Advanced Research Institute, CHA Bundang Medical Center, CHA University)
  • 투고 : 2022.09.05
  • 심사 : 2022.09.25
  • 발행 : 2023.02.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

키워드

과제정보

This work was supported by National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (No. 2021R1A2C1004571).

참고문헌

  1. Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature 1984;309:757-762 
  2. Gomes AQ, Martins DS, Silva-Santos B. Targeting γδ T lymphocytes for cancer immunotherapy: from novel mechanistic insight to clinical application. Cancer Res 2010;70:10024-10027 
  3. Alnaggar M, Xu Y, Li J, He J, Chen J, Li M, Wu Q, Lin L, Liang Y, Wang X, Li J, Hu Y, Chen Y, Xu K, Wu Y, Yin Z. Allogenic Vγ9Vδ2 T cell as new potential immunotherapy drug for solid tumor: a case study for cholangiocarcinoma. J Immunother Cancer 2019;7:36 
  4. Yazdanifar M, Barbarito G, Bertaina A, Airoldi I. γδ T cells: the ideal tool for cancer immunotherapy. Cells 2020;9:1305 
  5. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017;377:2531-2544 
  6. Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med 2020;382:545-553 
  7. Lanier LL. Shades of grey--the blurring view of innate and adaptive immunity. Nat Rev Immunol 2013;13:73-74 
  8. Li R, Johnson R, Yu G, McKenna DH, Hubel A. Preservation of cell-based immunotherapies for clinical trials. Cytotherapy 2019;21:943-957 
  9. Vantourout P, Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat Rev Immunol 2013;13:88-100 
  10. Rincon-Orozco B, Kunzmann V, Wrobel P, Kabelitz D, Steinle A, Herrmann T. Activation of V gamma 9V delta 2 T cells by NKG2D. J Immunol 2005;175:2144-2151 
  11. Wiemann K, Mittrucker HW, Feger U, Welte SA, Yokoyama WM, Spies T, Rammensee HG, Steinle A. Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo. J Immunol 2005;175:720-729 
  12. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999;285:727-729 
  13. Kong Y, Cao W, Xi X, Ma C, Cui L, He W. The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D. Blood 2009;114:310-317 
  14. Cho HW, Kim SY, Sohn DH, Lee MJ, Park MY, Sohn HJ, Cho HI, Kim TG. Triple costimulation via CD80, 4-1BB, and CD83 ligand elicits the long-term growth of Vγ9Vδ2 T cells in low levels of IL-2. J Leukoc Biol 2016;99:521-529 
  15. Dieli F, Vermijlen D, Fulfaro F, Caccamo N, Meraviglia S, Cicero G, Roberts A, Buccheri S, D'Asaro M, Gebbia N, Salerno A, Eberl M, Hayday AC. Targeting human γδ T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer. Cancer Res 2007;67:7450-7457 
  16. Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA, Yang Y, Becker MS, Zanetta L, Dejana E, Gasson JC, Tallquist MD, Iruela-Arispe ML. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 2008;3:625-636 
  17. Timmermans F, Velghe I, Vanwalleghem L, De Smedt M, Van Coppernolle S, Taghon T, Moore HD, Leclercq G, Langerak AW, Kerre T, Plum J, Vandekerckhove B. Generation of T cells from human embryonic stem cell-derived hematopoietic zones. J Immunol 2009;182:6879-6888 
  18. Chang CW, Lai YS, Lamb LS Jr, Townes TM. Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells. PLoS One 2014;9:e97335 
  19. Zhong C, Zhu J. Transcriptional regulators dictate innate lymphoid cell fates. Protein Cell 2017;8:242-254 
  20. Laurenti E, Doulatov S, Zandi S, Plumb I, Chen J, April C, Fan JB, Dick JE. The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment. Nat Immunol 2013;14:756-763 
  21. Di Marco Barros R, Roberts NA, Dart RJ, Vantourout P, Jandke A, Nussbaumer O, Deban L, Cipolat S, Hart R, Iannitto ML, Laing A, Spencer-Dene B, East P, Gibbons D, Irving PM, Pereira P, Steinhoff U, Hayday A. Epithelia use butyrophilin-like molecules to shape organ-specific γδ T cell compartments. Cell 2016;167:203-218.e17 
  22. Cano CE, Pasero C, De Gassart A, Kerneur C, Gabriac M, Fullana M, Granarolo E, Hoet R, Scotet E, Rafia C, Herrmann T, Imbert C, Gorvel L, Vey N, Briantais A, le Floch AC, Olive D. BTN2A1, an immune checkpoint targeting Vγ9Vδ2 T cell cytotoxicity against malignant cells. Cell Rep 2021;36:109359 
  23. Paczulla AM, Rothfelder K, Raffel S, Konantz M, Steinbacher J, Wang H, Tandler C, Mbarga M, Schaefer T, Falcone M, Nievergall E, Dorfel D, Hanns P, Passweg JR, Lutz C, Schwaller J, Zeiser R, Blazar BR, Caligiuri MA, Dirnhofer S, Lundberg P, Kanz L, Quintanilla-Martinez L, Steinle A, Trumpp A, Salih HR, Lengerke C. Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion. Nature 2019;572:254-259 Erratum in: Nature 2019;572:E19 
  24. Silva-Santos B, Serre K, Norell H. γδ T cells in cancer. Nat Rev Immunol 2015;15:683-691 
  25. Themeli M, Kloss CC, Ciriello G, Fedorov VD, Perna F, Gonen M, Sadelain M. Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat Biotechnol 2013;31:928-933 
  26. Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell 2018;23:181-192.e5 
  27. Jing R, Scarfo I, Najia MA, Lummertz da Rocha E, Han A, Sanborn M, Bingham T, Kubaczka C, Jha DK, Falchetti M, Schlaeger TM, North TE, Maus MV, Daley GQ. EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity. Cell Stem Cell 2022;29:1181-1196.e6 
  28. Straetemans T, Kierkels GJJ, Doorn R, Jansen K, Heijhuurs S, Dos Santos JM, van Muyden ADD, Vie H, Clemenceau B, Raymakers R, de Witte M, Sebestyen Z, Kuball J. GMP-grade manufacturing of T cells engineered to express a defined γδTCR. Front Immunol 2018;9:1062