Gamma Delta T Cells in the Tumour Microenvironment: A Double-Edged Sword

Area of Science:

• Immunology
• Cancer Biology
• Cellular Therapy

Background:

• Gamma delta (γδ) T cells are a unique lymphocyte subset with dual roles in cancer immunity.
• Their function is critically influenced by the tumor microenvironment (TME), acting as a double-edged sword.
• γδ T cells recognize stress-induced antigens independently of MHC, enabling rapid immunosurveillance.

Purpose of the Study:

• To critically review the dichotomous roles of γδ T cells in cancer immunosurveillance.
• To analyze their tumor-suppressive and tumor-promoting functions within the TME.
• To discuss emerging therapeutic strategies targeting γδ T cells for cancer immunotherapy.

Main Methods:

• Literature review and critical analysis of existing research on γδ T cell function in cancer.
• Examination of specific γδ T cell subsets (e.g., Vγ9Vδ2, Vδ1) and their mechanisms of action.
• Discussion of the impact of the tumor microenvironment on γδ T cell polarization.

Main Results:

• Vγ9Vδ2 T cells exhibit potent anti-tumorigenic effects via cytotoxicity (perforin, granzyme) and IFN-γ secretion.
• Certain γδ T cell subsets, like IL-17-producing Vδ1 T cells, can promote tumor growth by fostering immunosuppression and angiogenesis.
• The TME significantly dictates whether γδ T cells act in a pro- or anti-tumorigenic manner.

Conclusions:

• The dual function of γδ T cells presents challenges and opportunities for cancer immunotherapy.
• Understanding the molecular regulation of γδ T cell function is crucial for therapeutic development.
• Strategies like CAR-γδ T cell therapy and combination approaches with immune checkpoint inhibitors show promise for enhancing anti-cancer immunity.