Flow cytometric assessment of autologous gammadelta T cells in patients with acute myeloid leukemia: potential effector cells for immunotherapy?
BACKGROUND
Gammadelta 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 gammadelta T cells in AML. The aim of the study was to enumerate peripheral blood gammadelta T cells in patients with AML and explore the feasibility of their use clinically.


METHODS
We compared the absolute circulating gammadelta T cell levels in 33 AML patients before and after treatment versus 20 healthy volunteers using flow cytometry. The function of gammadelta 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 gammadelta T cell levels compared with healthy controls: median 38/microL versus 83/microL; P = 0.051. Sequential gammadelta 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/microL versus 105/microL; P = 0.008. Patients with residual disease had significantly higher gammadelta T cell counts compared to those retested after they had achieved complete remission (CR); P = 0.0025. In CR, gammadelta T cell counts remained lower than those of healthy individuals: median 33/microL versus 83/microL, P = 0.030. We detected a sharp increase (on average, four-fold higher than values in CR) of gammadelta T cells in patients in very early morphologic or molecular relapse. We also tested the functional properties of gammadelta T cells from patients with AML in CR. Flow cytometric assessment of IFN-gamma revealed similar numbers of gammadelta T cells expressing the T1 cytokine compared with healthy controls. We also showed that gammadelta T cells were able to kill leukemic target cells in vitro.


CONCLUSIONS
Flow cytometric assessment of gammadelta T cells in patients with AML revealed quantitative shifts with respect to disease status. Our data suggest that gammadelta T cells warrant further investigation as potential therapeutic agents.
Aswald
Jorg M
JM
Department of Medical Oncology and Hematology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9.
Wang
Xing-Hua
XH
Aswald
Sandra
S
Lutynski
Andrzej
A
Minden
Mark D
MD
Messner
Hans A
HA
Keating
Armand
A
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012008:Recurrence; D012074:Remission Induction; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta