Senior Group Kabelitz

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. 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 (1). 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 (2).

Our group investigates the modulation of activation and effector activity of human γδ T cells by epigenetic modifiers like Vitamin C (3,4), and by ligands for innate immune receptors like TLR8 (5) and cGAS/STING. Both TLR and STING ligands are in clinical studies as adjuvants to enhance the anti-tumor immune response. We hope that our investigations will contribute to design strategies for optimization of γδ T-cell based cancer immunotherapy.

Our results indicate tat the costimulating activity of STING ligands on human γδ T-cell activation is primarily an indirect mechanism depending on the presence of monocytes. Therefore, we also study the differentiation potential of human monocytes in response to several newly developed STING ligands.

• Modulation of γδ T-cell activation by Vitamin C, TLR/STING ligands, as well as Site-Specific Immunomodulators
• Metabolic modulation of γδ T-cell activation
• Plasticity of monocyte differentiation in response to cGAS/STING activation

1. 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
2. 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
3. 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.
4. Serrano R, Wesch D, Kabelitz D. Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes. 2020; 9,713
5. 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

Prof. Dr. Dieter Kabelitz

• PUBMED
• PUBLONS

Dr. rer. nat. Christian Peters

• PUBLONS
• ORCID

• Fritz-Thyssen Foundation
• Wilhem-Sander Foundation.
• DFG
• DAAD (German Academic Exchange Service)

• Prof. Dieter Adam, Institute of Immunology, University of Kiel
• Dr. Jaydeep Bhat, University of Bochum
• Prof. Gunther Hartmann, University of Bonn
• Dr. Shirin Kalyan, University of British Columbia, Vancouver, Canada
• PD Dr. Marcus Lettau, Institute of Immunology, University of Kiel
• Prof. Wolfgang Schamel, University of Freiburg
• Prof. Wenwei Tu, University of Hong Kong
• Prof. Daniela Wesch, Institute of Immunology, University of Kiel
• Prof. Zhinan Yin, Jinan University, Guangzhou, China