Immunotherapy Research Group

γδ T cells constitute 1–10% of circulating T lymphocytes and are considered enigmatic cells that bridge innate and adaptive immune responses.

This feature makes them more suitable for immunotherapeutic applications than the dominant αβ T lymphocytes, which require antigen processing and presentation by major histocompatibility complex (MHC) molecules. γδ T-cell receptors (γδ TCRs) can directly recognize stress antigens without MHC involvement.

Importantly, the lack of MHC restriction allows allogeneic use of γδ T cells in situations where expansion of autologous T cells is difficult or impossible. Upon activation, γδ T cells secrete interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α)—cytokines known for their cytotoxic properties.

The second major γδ T-cell subpopulation, containing the Vδ1 chain and found mainly in the skin and mucosal tissues, recognizes molecules present on stressed and cancerous cells, such as MICA/B and UL16-binding proteins. Both γδ T-cell populations also express NKG2D, another receptor that recognizes stress antigens such as MICA/B and powerfully activates anticancer functions.

Extensive preclinical data from mouse studies have demonstrated the effectiveness of γδ T cells derived from blood and expanded in vitro against various tumor types, enabling their further evaluation in early-phase clinical trials.

Despite the identification of certain ligands for the γδ TCR, the mechanisms governing γδ T-cell activation are still not fully understood.

Despite the identification of several γδ TCR ligands, the mechanisms of γδ T-cell activation are still not fully understood. It remains unclear which molecules—beyond the γδ TCR itself—are essential for their activation. Our goal is to investigate γδ TCR-mediated signaling and the mechanisms governing γδ T-cell activation, which may enable the development of more effective effector cells for cancer therapy.

We also plan to genetically modify γδ T cells to enhance their anticancer properties. Our ultimate aim is to develop a patented medicinal product based on γδ T cells, which will reach clinical use and help oncology patients.

Research plan

Using in vitro cultures of blood-derived γδ T cells, we assess their cytotoxic activity against cancer cell lines and primary tumor cells obtained from patients, in order to determine which subpopulation (Vδ2+ or Vδ1+) is best suited for therapeutic applications.

We are creating three-dimensional cancer cell cultures to study and compare the anticancer efficacy of γδ T cells. In the next phase, the effectiveness of these cells will be verified in vivo in a mouse model.