Expanded Human Blood-Derived γδT Cells Display Potent Antigen-Presentation Functions

Area of Science:

• Immunology
• Cellular Therapy
• Cancer Research

Background:

• Cell-based immunotherapy utilizes effector cells or endogenous immunity mobilization.
• Dendritic cells (DCs) are commonly used, often derived from monocytes.
• Human gamma delta T (γδT) cells can become potent antigen-presenting cells (APCs) called γδT-APCs.

Purpose of the Study:

• To optimize the expansion of γδT cells for use as a cellular vaccine.
• To assess the functionality and antigen-presenting capabilities of expanded γδT cells.
• To evaluate the potential of γδT-APCs in cancer immunotherapy.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from healthy individuals and melanoma patients were stimulated with zoledronate.
• Cells were cultured for 14 days with IL-2 and IL-15 to expand γδT cells.
• Functionality was assessed via tumor cell killing, cytokine secretion, proliferation, and APC marker expression.

Main Results:

• Optimal γδT cell expansion (>10^7 cells/ml) was achieved using zoledronate, IL-2, and IL-15.
• Expanded γδT cells (day 14) exhibited effector memory αβT (TEM) cell characteristics and retained tumor-killing and cytokine-secreting functions.
• Day 14 γδT cells expressed APC markers and demonstrated potent in vitro APC functions, including cross-presentation of protein antigens to CD8(+) αβT cells.

Conclusions:

• Day 14 γδT cell cultures provide a scalable source of functional autologous APCs.
• These γδT-APC cultures are effective in stimulating anti-tumor immune responses.
• This approach offers a promising new strategy for immunotherapy in various cancers.