Senior Group Kabelitz

 / Research

Senior Group Kabelitz

The Kabelitz group investigates the modulation of activation and effector activity of human γδ T cells by vitamins (e.g., vitamin C), selected cytokines, and ligands for the Notch receptor. Our goal is to improve and optimize the effector function of γδ T cells for future clinical application in cancer immunotherapy.

Group leader:

Dieter 
Kabelitz

Prof. Dr. med.

Group members:

Lea  
Cierna
Daniel  
Gombert
Yasmin 
Optaczy

M.Sc.
Hayley 
Reid

PhD
Jara 
Simeonov

In contrast to conventional CD4 and CD8 T cells, γδ T cells do not recognize peptides but rather intermediates of the cholesterol metabolism (pyrophosphates) which are overproduced by tumor cells in comparison to healthy cells. As a consequence, γδ T cells can recognize and kill tumor cells independently of HLA molecules, which makes γδ T cells attractive effector cells for immunotherapy (1,2). Importantly, it has been already shown that γδ T cells can be safely isolated from allogeneic healthy donors for subsequent adoptive transfer into cancer patients (3). On the other hand, it is obvious that the effector function of γδ T cells requires optimization in order to improve the clinical efficacy of γδ T-cell based cancer immunotherapy (1,4).

Our group investigates the modulation of activation and effector activity of human γδ T cells by vitamins including vitamin C (5,6,7), and by ligands for the Notch receptor and cGAS/STING (8,9). We have developed short-term activation assays to investigate the γδ T-cell responsiveness to different stimuli (10), and we also study the functional capacity of γδ T cells in tuberculosis and acute influenza infections.

  • Modulation of γδ T cell activation by Notch ligands and selected cytokines
  • Molecular analysis of γδ T cell modulation by vitamin C
  • In vitro modulation of immune cell activation by various vitamins and their derivatives
  1. Kabelitz D, Zeissig S. γδ T cells in colorectal and liver cancer. Nat Rev Gastroenterol Hepatol. 2026 Apr 22. doi: 10.1038/s41575-026-01196-7. Epub ahead of print.
  2. Hu Y, Hu Q, Li Y, Lu L, Xiang Z, Yin Z, Kabelitz D, Wu Y. γδ T cells: origin and fate, subsets, diseases and immunotherapy. Signal Transduct Target Ther. 2023 Nov 22;8(1):434. doi: 10.1038/s41392-023-01653-8.
  3. Xu Y, Xiang Z, Alnaggar M, Kouakanou L, Li J, He J, Yang J, Hu Y, Chen Y, Lin L, Hao J, Li J, Chen J, Li M, Wu Q, Peters C, Zhou Q, Li J, Liang Y, Wang X, Han B, Ma M, Kabelitz D, Xu K, Tu W, Wu Y, Yin Z. Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs survival of patients with late-stage lung and liver Cancer. Cell Mol Immunol. 2021; 18: 427-439
  4. Kabelitz D, Serrano R, Kouakanou L, Peters C, Kalyan S. Cancer immunotherapy with γδ T cells: many paths ahead of us. Cell Mol Immunol. 2020;17:925-939
  5. Kabelitz D, Cierna L, Juraske C, Zarobkiewicz M, Schamel WW, Peters C. Empowering γδ T-cell functionality with vitamin C. Eur J Immunol. 2024 Jul;54(7):e2451028. doi: 10.1002/eji.202451028.
  6. Kouakanou L, Peters C, Sun Q, Floess S, Bhat J, Huehn J, Kabelitz D. Vitamin C supports conversion of human γδ T cells into FOXP3-expressing regulatory cells by epigenetic regulation. Sci Rep. 2020; 10, 6550.
  7. Kouakanou L, Xu Y, Peters C, He J, Wu Y, Yin Z, Kabelitz D. Vitamin C promotes the proliferation and effector functions of human γδ T cells. Cell Mol Immunol. 2020;17:462-473. doi: 10.1038/s41423-019-0247-8
  8. Serrano R, Lettau M, Zarobkiewicz M, Wesch D, Peters C, Kabelitz D. Stimulatory and inhibitory activity of STING ligands on tumor-reactive human gamma/delta T cells. Oncoimmunology. 2022;11:2030021. doi: 10.1080/2162402X.2022.2030021.
  9. Luo J, Wang S, Yang Q, Fu Q, Zhu C, Li T, Yang S, Zhao Y, Guo R, Ben X, Zheng Y, Li S, Yang G, Zhang H, Xiao H, Jiang Z, Yan N, Kabelitz D, Sun G, Granot Z, Lu L, You F, Hao J, Yin Z. γδ T Cell-mediated Tumor Immunity is Tightly Regulated by STING and TGF-β Signaling Pathways. Adv Sci (Weinh). 2025 Jan;12(2):e2404432. doi: 10.1002/advs.202404432.
  10. Gombert D, Simeonov J, Klein K, Agaugué S, Scheffold A, Kabelitz D, Peters C. Butyrophilin 3A/2A1-independent activation of human Vγ9Vδ2 γδ T cells by bacteria. PNAS Nexus. 2025;4:pgaf358. doi: 10.1093/pnasnexus/pgaf358.

Prof. Dr. Dieter Kabelitz

 

Dr. rer. nat. Christian Peters

  • DFG (Ka 502/19-3)
  • Imcheck Therapeutics (France)
  • dsm Firmenich (Switzerland)
  • Dr. Jaydeep Bhat, DKFZ Heidelberg
  • Prof. Wolfgang Schamel, University of Freiburg
  • Prof. Matthias Peipp, Division of Antibody-Based Immunotherapy, Department of Internal Medicine II, UKSH Campus Kiel
  • Prof. Zhinan Yin, Jinan University, Guangzhou, China