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

Cytotherapy. 2013 Apr;15(4):481-91. doi: 10.1016/j.jcyt.2012.12.004. Epub 2013 Feb 5.


Background aims: Adoptive immunotherapy is emerging as a potent anti-tumor treatment modality; Vγ9Vδ2 T cells may represent appropriate agents for such cancer immunotherapy. To improve the currently limited success of Vγ9Vδ2 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 Vγ9δ2 T cell in vivo survival.

Methods: We conducted a clinical trial of adoptive Vγ9Vδ2 T-cell transfer therapy in six colorectal cancer patients who received pulmonary metastasectomy. Patients' peripheral blood mononuclear cells were stimulated with zoledronate (5 μmol/L) and IL-2 (1000 IU/mL) for 14 d. Harvested cells, mostly Vγ9Vδ2 T cells, were given intravenously weekly without additional IL-2 eight times in total. The frequency, phenotype and common γ-chain cytokine receptor expression of Vγ9Vδ2 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 Vγ9Vδ2 T cells expanded well without exogenous IL-2 administration or lymphodepleting preconditioning. They maintained effector functions in terms of interferon-γ secretion and prompt release of cytotoxic granules in response to PMA/ionomycin or isopentenyl pyrophosphate-positive cells. Because they are IL-2Rα(-)IL-7Rα(-)IL-15Rα(-)IL-2Rβ(+)γc(+), 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 Vγ9Vδ2 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Proliferation
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / therapy*
  • Diphosphonates / pharmacology
  • Female
  • Humans
  • Imidazoles / pharmacology
  • Immunotherapy, Adoptive / methods*
  • Interleukin Receptor Common gamma Subunit / biosynthesis
  • Interleukin Receptor Common gamma Subunit / immunology*
  • Interleukin-15 / immunology
  • Interleukin-2 / pharmacology
  • Interleukin-2 Receptor beta Subunit / biosynthesis
  • Interleukin-2 Receptor beta Subunit / immunology*
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / transplantation*
  • Zoledronic Acid


  • Diphosphonates
  • Imidazoles
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15
  • Interleukin-2
  • Interleukin-2 Receptor beta Subunit
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid