The Duality of Tumor-Associated γδ T Cells

In the intricate realm of cancer immunity, the emerging spotlight shines brightly on γδ T cells. In recent years, researchers have uncovered an intriguing duality within tumor-associated γδ T cells—a behavior that can either foster tumor progression or instigate antitumor immunity.

Creative Biolabs delves into the captivating world of tumor-associated γδ T cells, exploring their paradoxical roles as both facilitators and suppressors of cancer. We are committed to harnessing its duality to help researchers develop cutting-edge therapies.

Tumor-Promoting Functions of γδ T Cells

Tumor microenvironments are masterful at exploiting immune cells to aid cancer growth. Among them, certain subsets of γδ T cells have been found to exert protumoral effects, fueling the cancer's survival and dissemination. These γδ T cells can contribute to tumor-promoting activities through various mechanisms:

• Production of pro-inflammatory cytokines: Some γδ T cells secrete pro-inflammatory cytokines like IL-17 and TNF-α, which create an immunosuppressive environment and promote tumor cell survival.
• Induction of angiogenesis: Tumor-associated γδ T cells can secrete factors that stimulate angiogenesis, facilitating the formation of new blood vessels to supply nutrients to the growing tumor mass.
• Immunosuppression via regulatory T cells: γδ T cells can indirectly support tumor growth by promoting the expansion of regulatory T cells (Tregs) that suppress antitumor immune responses.

Fig. 1 γδ T cells promote tumor development. (Li Y, et al., 2021)

Antitumor Functions of γδ T Cells

On the other side of the coin, γδ T cells have demonstrated robust antitumor capabilities, contributing to tumor eradication and immune surveillance. This positive aspect of tumor-associated γδ T cells is particularly prominent when considering specific subsets.

• Cytotoxicity against tumor cells: Certain γδ T cell subsets possess potent cytotoxic properties, directly recognizing and eliminating tumor cells in a major histocompatibility complex (MHC)-independent manner.
• Activation of other immune cells: γδ T cells can promote antitumor immune responses by engaging with and activating other immune cell populations, such as dendritic cells, natural killer cells, and conventional αβ T cells.
• Modulation of immune checkpoints: Some γδ T cells express immune checkpoint molecules, suggesting their potential in checkpoint blockade therapies.

Fig. 2 γδ T cells enhance the anti-tumor ability of other immune cells. (Li Y, et al., 2021)

Factors Influencing the Duality

The factors that dictate whether tumor-associated γδ T cells display various behaviors are complex and multifaceted. Several critical determinants that contribute to this duality include:

• Tumor Microenvironment
• Tumor Type and Stage
• Tumor Mutational Burden

Harnessing the Duality for Immunotherapy

Understanding the dual role of tumor-associated γδ T cells holds significant promise for developing innovative cancer immunotherapies. Researchers are actively exploring ways to modulate these cells to elicit potent antitumor responses while mitigating their pro-tumoral functions.

• γδ T Cell-Based Therapies

Adoptive cell transfer of ex vivo-expanded tumor-reactive γδ T cells shows promise as a targeted and personalized immunotherapeutic approach.

• Combination Therapies

Combining γδ T cell-based therapies with immune checkpoint inhibitors or other immunomodulatory agents may enhance treatment efficacy.

• Engineering γδ T Cells

Genetic engineering approaches could be employed to enhance the cytotoxicity and persistence of tumor-targeting γδ T cells.

Gaining a comprehensive understanding of the factors that dictate this duality holds the key to unlocking their potential in cancer immunotherapy. Creative Biolabs is dedicated to providing innovative γδ T cell solutions that facilitate a robust and durable anti-tumor immune response. For a more detailed service plan, contact us immediately.

References

1. Li Y, et al. The dual roles of human γδ T cells: anti-tumor or tumor-promoting. Frontiers in immunology, 2021, 11: 619954.
2. Lo Presti E, et al. γδ T cells and tumor microenvironment: from immunosurveillance to tumor evasion. Frontiers in immunology, 2018, 9: 1395.