Flow cytometric assessment of autologous γδ T cells in patients with acute myeloid leukemia:: Potential effector cells for immunotherapy?

Background: gamma delta T cells are a rare component of the circulating innate immune system capable of exerting anti-neoplastic activity. This population may be suitable for the adoptive immunotherapy of acute myeloid leukemia (AML). Little is known however, about the frequency and function of circulating gamma delta T cells in AML. The aim of the study was to enumerate peripheral blood gamma delta T cells in patients with AML and explore the feasibility of their use clinically. Methods: We compared the absolute circulating gamma delta T cell levels in 33 AML patients before and after treatment versus 20 healthy volunteers using flow cytometry. The function of gamma delta T cells was assessed by detection of intracelluar interferon-gamma (IFN-gamma) and cytotoxicity against leukemic blasts. Results: AML patients with high blast counts prior to induction chemotherapy had marginally decreased gamma delta T cell levels compared with healthy controls: median 38/mu L versus 83/mu L; P = 0.051. Sequential gamma delta T cell enumeration after induction showed significantly decreased counts in patients with a persistently high blast burden compared to patients with reduced but detectable residual disease (molecular maker or borderline bone marrow infiltration): median 7/mu L versus 105/mu L; P = 0.008. Patients with residual disease had significantly higher gamma delta T cell counts compared to those retested after they had achieved complete remission (CR); P = 0.0025. In CR, gamma delta T cell counts remained lower than those of healthy individuals: median 33/mu L versus 83/mu L, P = 0.030. We detected a sharp increase (on average, four-fold higher than values in CR) of gamma delta T cells in patients in very early morphologic or molecular relapse. We also tested the functional properties of gamma delta T cells from patients with AML in CR. Flow cytometric assessment of IFN-gamma revealed similar numbers of gamma delta T cells expressing the T1 cytokine compared with healthy controls. We also showed that gamma delta T cells were able to kill leukemic target cells in vitro. Conclusion: Flow cytometric assessment of gamma delta T cells in patients with AML revealed quantitative shifts with respect to disease status. Our data suggest that gamma delta T cells warrant further investigation as potential therapeutic agents. (c) 2006 International Society for Analytical Cytology.