Production of tumour-derived suppressor factor in patients with acute myeloid leukaemia.
In an attempt to investigate the underlying cause of impaired cellular cytotoxic functions in patients with acute myeloid leukaemia and the relative ineffectiveness of immunotherapy with recombinant interleukin 2 (IL-2), normal donor lymphocytes were incubated in AML sera and in supernatant of myeloblasts. There was significant inhibition of both the natural killer activity and the lectin dependent cellular cytotoxicity of the normal donor lymphocytes compared to when incubation took place in autologous or normal allogeneic sera or marrow supernatant. This inhibition was time-related and partially reversible by washing of the normal lymphocytes immediately before the cytotoxicity assay. The suppressor factor, however, did not inhibit the IL-2 induced lymphocyte proliferation or affect the cytotoxicity-linked cytoplasmic serine esterase expression in the normal lymphocytes. This suppressor phenomenon was of myeloblast origin. Chronic exposure to the tumour-derived suppressor factor may be responsible for the impaired cellular cytotoxic functions observed in patients with acute myeloid leukaemia. It may also suppress the in vivo cytotoxic functions of IL-2 activated lymphocytes in patients treated with recombinant IL-2, hence leading to the disappointing results of immunotherapy so often encountered in clinical setting.
Lim
S H
SH
Department of Haematology, University College Hospital, London, U.K.
Worman
C P
CP
Jewell
A
A
Goldstone
A H
AH
D003602:Cytotoxicity, Immunologic; D004950:Esterases / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis*; D013997:Time Factors
D007376:Interleukin-2; D013491:Suppressor Factors, Immunologic; D004950:Esterases; C022635:serine esterase