From the Guidelines
Gamma delta T cells are a promising area of research for immunotherapy, particularly in cancer treatment, due to their ability to recognize and kill transformed cells without prior sensitization, as supported by recent studies 1.
Key Characteristics of Gamma Delta T Cells
- Represent approximately 1-5% of circulating T cells in humans
- Express unique T cell receptors composed of gamma and delta chains
- Recognize antigens directly without requiring presentation by major histocompatibility complex (MHC) molecules
- Function at the interface between innate and adaptive immunity, responding rapidly to infection and cellular stress
- Abundant in epithelial tissues like the skin, intestine, and reproductive tract, serving as a first line of defense
- Recognize phosphoantigens produced by bacteria and stressed or transformed host cells, enabling participation in antimicrobial immunity, tumor surveillance, and tissue repair
- Produce cytokines like interferon-gamma and interleukin-17, contributing to inflammation regulation
Potential Applications in Immunotherapy
- Direct recognition and killing of transformed cells without prior sensitization
- Potential use in cancer treatment, particularly in combination with other immunotherapies
- Research interest has grown due to their potential applications in immunotherapy for cancer and infectious diseases
Recent Studies and Findings
- Studies have shown that gamma delta T cells can be used to target specific antigens, such as CD19, in cancer cells 1
- CAR T-cell therapy has been associated with cytokine release syndrome (CRS), which can trigger cardiotoxicity and atrial fibrillation 1
- The use of gamma delta T cells in immunotherapy is still in its early stages, and further research is needed to fully understand their potential and limitations.
From the Research
Characteristics of Gamma Delta T Cells
- Gamma delta T cells have the ability to kill tumor cells in a major histocompatibility complex (MHC)-unrestricted manner, making them a potential candidate for cancer immunotherapy 2, 3.
- The Vγ9Vδ2 T cell subset is the major gamma delta T cell subset in humans and is activated by intermediates of isoprenoid biosynthesis or aminobisphosphonate inhibitors of farnesyldiphosphate synthase 3, 4.
- Activated gamma delta T cells release copious amounts of interferon (IFN)-γ and tumor necrosis factor (TNF)-α and exhibit potent anti-tumor activity 5, 4.
Expansion and Activation of Gamma Delta T Cells
- Zoledronate, an aminobisphosphonate, can be used to activate and expand gamma delta T cells from cancer patients for use in adoptive immunotherapy 2, 5.
- The combination of zoledronate and interleukin-2 (IL-2) can induce a significant long-term shift of peripheral gamma delta cells toward an activated effector-memory-like state, producing IFN-γ and perforin 5.
- Gamma delta T cells can be expanded in vitro and can exert potent cytotoxicity, making them a potential candidate for autologous cellular immunotherapy of cancer 2.
Clinical Applications of Gamma Delta T Cells
- Gamma delta T cell-based immune checkpoint therapy is an attractive candidate for antitumor treatment, as gamma delta T cells have the ability to respond to immune checkpoint inhibitors (ICIs) and can be used to improve antitumor effects 6.
- Clinical trials have shown that targeting gamma delta T cells can induce immunologic and clinical responses in patients with metastatic carcinomas, and that gamma delta cell phenotypes and serum TRAIL may constitute novel biomarkers of prognosis upon therapy 5.
- The use of gamma delta T cells in combination with therapeutic monoclonal antibodies can efficiently mediate antibody-dependent cellular cytotoxicity against tumors, making them a potential candidate for cancer immunotherapy 4.