Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain and the common γ-chain

Background aims. Adoptive immunotherapy is emerging as a potent anti-tumor treatment modality; V gamma 9V delta 2 T cells may represent appropriate agents for such cancer immunotherapy. To improve the currently limited success of V gamma 9V delta 2 T-cell-based immunotherapy, we examined the in vivo dynamics of these adoptively-transferred cells and hypothesized that interleukin (IL)-15 is the potential factor for V gamma 9 delta 2 T cell in vivo survival. Methods. We conducted a clinical trial of adoptive V gamma 9V delta 2 T-cell transfer therapy in six colorectal cancer patients who received pulmonary metastasectomy. Patients' peripheral blood mononuclear cells were stimulated with zoledronate (5 mu mol/L) and IL-2 (1000 IU/mL) for 14 d. Harvested cells, mostly V gamma 9V delta 2 T cells, were given intravenously weekly without additional IL-2 eight times in total. The frequency, phenotype and common gamma-chain cytokine receptor expression of V gamma 9V delta 2 T cells in peripheral blood was monitored by flow cytometry at each time point during treatment and 4 and 12 weeks after the last administration. Results. Adoptively transferred V gamma 9V delta 2 T cells expanded well without exogenous IL-2 administration or lymphodepleting preconditioning. They maintained effector functions in terms of interferon-gamma secretion and prompt release of cytotoxic granules in response to PMA/ionomycin or isopentenyl pyrophosphate-positive cells. Because they are IL-2R alpha-IL-7R alpha-IL-15R alpha-IL-2R beta(+)gamma(+)(c), it is likely that IL-2 or IL-15 is required for their maintenance. Conclusions. The persistence of large numbers of functionally active adoptively transferred V gamma 9V delta 2 T cells in the absence of exogenous IL-2 implies that an endogenous factor, such as IL-15 transpresentation, is adequate to support these cells in vivo.