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Flow cytometric assessment of autologous γδ T cells in patients with acute myeloid leukemia: Potential effector cells for immunotherapy?
Author(s) -
Aswald Jorg M.,
Wang XingHua,
Aswald Sandra,
Lutynski Andrzej,
Minden Mark D.,
Messner Hans A.,
Keating Armand
Publication year - 2006
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.20115
Subject(s) - medicine , immunophenotyping , immunology , immunotherapy , bone marrow , myeloid , t cell , flow cytometry , myeloid leukemia , minimal residual disease , immune system , population , leukemia , environmental health
Background: γδ 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 γδ T cells in AML. The aim of the study was to enumerate peripheral blood γδ T cells in patients with AML and explore the feasibility of their use clinically. Methods: We compared the absolute circulating γδ T cell levels in 33 AML patients before and after treatment versus 20 healthy volunteers using flow cytometry. The function of γδ T cells was assessed by detection of intracelluar interferon‐γ (IFN‐γ) and cytotoxicity against leukemic blasts. Results: AML patients with high blast counts prior to induction chemotherapy had marginally decreased γδ T cell levels compared with healthy controls: median 38/μL versus 83/μL; P = 0.051. Sequential γδ 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/μL versus 105/μL; P = 0.008. Patients with residual disease had significantly higher γδ T cell counts compared to those retested after they had achieved complete remission (CR); P = 0.0025. In CR, γδ T cell counts remained lower than those of healthy individuals: median 33/μL versus 83/μL, P = 0.030. We detected a sharp increase (on average, four‐fold higher than values in CR) of γδ T cells in patients in very early morphologic or molecular relapse. We also tested the functional properties of γδ T cells from patients with AML in CR. Flow cytometric assessment of IFN‐γ revealed similar numbers of γδ T cells expressing the T1 cytokine compared with healthy controls. We also showed that γδ T cells were able to kill leukemic target cells in vitro. Conclusion: Flow cytometric assessment of γδ T cells in patients with AML revealed quantitative shifts with respect to disease status. Our data suggest that γδ T cells warrant further investigation as potential therapeutic agents. © 2006 International Society for Analytical Cytology