Cell-mediated cytotoxicity in relation to active immunotherapy in acute myeloid leukaemia

Summary Tests comparing lymphocytes from normal controls, remission AML patients not receiving immunotherapy, and AML immunotherapy patients showed that cell-mediated cytotoxicity (CMC) to allogeneic AML cells requires in vivo priming and in vitro stimulation by AML cells. An in vitro lymphoproliferative response to allogeneic AML cells correlated with the development of CMC in immunotherapy-primed lymphocytes, though proliferation did not always lead to CMC. This may be due to differences in the lytic susceptibility of different AML cells. AML-stimulated CMC was cross-reactive on normal allogeneic PHA-transformed lymphoblasts and on lymphoblastoid cell lines (LCL). There was extensive cross-reactivity on allogeneic AML targets not used as in vitro stimulators. However, LCL generally did not induce CMC to allogeneic AML cells. CMC was generally absent, except in a few tests, on autologous PHA-transformed lymphoblasts following in vitro stimulation with allogeneic AML cells. CMC on autologous AML cells was equivocal, with little evidence for cross-reactive tumour-associated antigens in AML. Whilst CMC in this system was correlated with in vivo priming by immunotherapy, it is unlikely that such restimulated lymphocytes are the mediators of host-leukaemic cell cytolysis in vivo.