Vδ2 γδ T Cells

Vδ2 chains are almost exclusively paired with the Vγ9 chains to form Vγ9Vδ2 γδ T cells which are predominant in peripheral blood (70%). Currently, more and more studies are focusing on the potential of Vγ9Vδ2 T cells in anti-tumor effects and development of Vγ9Vδ2 T-cell based immunotherapy.

Role of Vδ2 γδ T Cells in Tumor Progression

Vγ9Vδ2 γδ T cells have been revealed to play anti-tumor effects in multiple tumors including renal cell carcinoma, non-small-cell lung cancer, gastric cancer, and others. Vγ9Vδ2 T cells can recognize tumor cells by the binding of NKRs and tumor antigens. NKRs are expressed on the surface of tumor cells, typically include NKG2D and DNAX accessory molecule-1 (DNAM-1). These receptors can recognize the various antigens on human tumor cells such as MHC class I chain-related molecules (MICA, MICB) and six ULBP-binding proteins. Vγ9Vδ2 T cells have been indicated to recognize ULBP1 and ULBP4 on leukemia, lymphoma, and epithelial tumor cells and induced their cytotoxicity to tumor cells. Besides, Vγ9Vδ2 T cells are induced to express multiple markers of antigen-presenting cells (APC) such as MHC I and II molecules, co-stimulatory molecules (CD80, CD86), and adhesion receptors (CD11a, CD18, CD54) under the stimulation of phosphoantigens, thus enable them to behave like APCs and present antigens to αβ T cells. In addition, Vγ9Vδ2 T cells can produce some cytokines such as IL-2, IL-4, and IL-10, and promote the secretion of antibodies by B cells.

Fig.1 Anti-tumour versus protumor roles of mouse γδ T cells. (Silva-Santos, 2015)

Vγ9Vδ2 γδ T Cell Based Immunotherapy

Owing to the most important role of Vγ9Vδ2 T cells in anti-tumor activity, they have been developed as promising candidates for immunotherapy. Vγ9Vδ2 T cell based immunotherapy is based on adoptive transfer of ex vivo-expanded Vγ9Vδ2 T cells or in vivo stimulation with aminodicarbonates or synthetic phosphoantigens. Several clinical studies indicated that adoptive transfer of autologous or allogenic Vγ9Vδ2 T cells can not only kill a variety of tumor cells, but also promote and rescue the anti-tumor capacity of CD4+ and CD8+ T cells. Vγ9Vδ2 T cells stimulated by or phosphoantigens aminodicarbonates in vivo have also shown cytotoxicity to multiple tumor cells. However, experimental data showed the clinical response rate of in vivo stimulation is generally lower than adoptive transfer.

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Reference

1. Silva-Santos, B.; et al. γδ T cells in cancer. Nature Reviews Immunology. 2015,15(11): 683-691