γδ T Cell Subsets

γδ T cells are a population of innate-like T lymphocytes characterized by T-cell receptors (TCRs) composed of γ and δ chains. They are widely distributed in the peripheral blood (PB) and mucosal tissues. γδ T cells have been revealed to exert dual roles in tumor immunity. On the one hand, γδ T cells suppress tumor occurrence by multiple mechanisms, including cytotoxicity against infected or tumor cells, cytokine and chemokine production, antigen-presenting functions, and regulatory abilities. On the other hand, γδ T cells exert suppressive effects on antitumor responses.

Fig.1 Polarization and responses of human γδ T-cell subsets to tumors. (Wu, 2017)

γδ T Cell Subsets Based on Structure

Human γδ T cells can be divided into four major groups according to their TCR δ chain usage: Vδ1, Vδ2, Vδ3, and Vδ5 T cells.

• Vδ1+ γδ T cells

Vδ1 is paired with various Vγ chains such as Vγ2, Vγ3, Vγ4, Vγ5, Vγ8, and Vγ10, to form different γδ T cell subsets. Vδ1+ γδ T cells play an anti-tumor effect in multiple cancers, such as chronic lymphoid leukemia, breast cancer, and multiple myeloma.

• Vδ2+ γδ T cells

Vδ2 is almost exclusively paired with Vγ9 to form Vγ9Vδ2 T cells, which are uniquely activated by phosphoantigens. Vγ9Vδ2 T cells have been indicated a strong anti-tumor ability against various tumors such as cholangiocarcinoma, breast cancer, and other cancers.

• Vδ3+ γδ T cells

Vδ3+ γδ T cells mainly exist in healthy peripheral blood and the liver. Little research has been done on their effects on the tumor process.

• Vδ5+ γδ T cells

Vδ5 is paired with Vγ4 to form Vδ5 Vγ4 T cells.

γδ T Cell Subsets Based on Function

Similar to αβ T cells, γδ T cells can be divided into different subsets based on their different functions.

• Effector γδ T Cells

Effector γδ T cells include IFN-γ-producing cells, IL-17-producing γδ T cells, and Follicular T helper (TFH) cells. They are involved in the regulation of tumor progress directly. γδ T17 cells can produce IL-17 which is a pro-inflammatory factor and associated with the development of chronic tissue inflammation and autoimmune diseases.

• Regulatory γδ T Cells

Regulatory γδ T cells, also known as γδ Treg cells, have been shown to exert an immunosuppressive effect during tumor progression. They are enriched in tumor-infiltrating lymphocytes of several types of cancer. A study showed tumor-infiltrating γδ Treg cells suppressed T-cell responses and dendritic cells (DC) maturation. Besides, γδ Treg cells have been also revealed to induce the senescence of T cells and DCs in cancer progression.

Creative Biolabs has focused on the research of γδ T cells for several years. We can leverage our expertise and advanced biological research technologies to support a full range of γδ T cell research services, including the development of γδ T cell therapy, analysis of γδ T cell receptor, γδ T cell development, and γδ T cell engineering.

References

1. Wu, D.; et al. Human γδ T-cell subsets and their involvement in tumor immunity. Cellular & Molecular Immunology. 2017, 14: 245-253.
2. Liu, Y.; Zhang, C. The role of human γδ T cells in anti-tumor immunity and their potential for cancer immunotherapy. Cells. 2020, 9: 1206