What are γδ T cells?
Gamma delta T lymphocytes (γδ T cells or γδ T lymphocytes), alongside alpha beta T lymphocytes (αβ T-cells) and B Lymphocytes, form a critical and highly conserved triumverate of the adaptive immune system. These cells act at the interface of the innate and adaptive immune systems, recognising molecular patterns of dysregulation in stressed, pathogen infected or transformed cells and rapidly responding to maintain homeostasis. γδ T lymphocytes are capable of eradicating cancerous or infected cells and triggering a systemic response via the adaptive immune system, without harming healthy cells.
Unlike other types of T lymphocyte, γδ T cells identify target cells via mechanisms that are independent of Major Histocompatibility Complex (MHC) protein presentation. Consequently, tumour cells cannot evade detection by downregulating MHC protein expression in response to treatment. This property also means that γδ T cells do not require prior antigen priming, have equal potential for killing tumours cells with low mutational loads, are less likely to be affected by therapeutic resistance issues and are suitable for allogeneic therapy as they are not limited by patient-specific factors as are autologous therapies.
Recent studies indicate that γδ T cells play an important role in anti-tumour responses. A bioinformatic study of large number of solid tumour samples showed that, amongst all different immune cell types, γδ T cell infiltration correlated highest with survival(1). A retrospective study of acute leukaemia patients receiving αβ T cell depleted allogeneic stem cell transplant (ASCT) showed that event free and overall survival correlated strongly with expansion of donor-derived γδ T cells(2). These results were confirmed recently by another laboratory in a prospective study which also showed that patients with high concentrations of γδ T cells two months after ASCT had lower incidence of acute graft versus host disease(3).
1. Gentles et al. Nat Med. 2015 Aug; 21(8):938-945
2. Godder et al. Bone Marrow Transplant. 2007 Jun; 39(12):751-7
3. Minculescu et al. Front Immunol. 2019 Aug 22; 10:1997