Differential modulation of immune recognition molecules by interleukin-7 in human acute leukaemias

Clinical animal models and in vitro data afford evidence for anti-leukaemia immunity. Many reports have underlined the interest of interleukin-7 (IL-7 ) use in cancer and its pivotal role in immune recognition, This cytokine, initially identified as a B cell growth factor, enhances the anti-tumour pr operties of immune effector cells via T lymphocyte activation, increased sp ecific cytotoxicity and cytokine secretion, Nonetheless, few data are avail able regarding the effect of IL-7 on the expression at the leukaemia cell s urface of molecules involved in the immune response, which defective expres sion could induce tolerance or anergy, This prompted us to study the effect s of IL-7 on 20 cases of acute myeloid leukaemia (AML) and 9 cases of lymph oid leukaemia (ALL), in comparison with gamma-interferon, a potent inducer of immune regulation molecule expression. In AML and ALL, IL-7 increased MH C class I molecule expression, while class II molecules were weakly modifie d, The expression of the tumour necrosis factor family members CD40 and Fas /CD95, together with the adhesion molecules ICAM-1/CD54 and CD58/LFA-3, was also increased in both types of leukaemia. The IL-7 was an efficient induc er of B7-2/CD86 expression in AML and ALL, while increased expression of B7 -1/CD80 was only observed in AML, In the corresponding, co-cultured T lymph ocyte population, IL-7 more particularly increased B7-1/CD80 and CD58/LFA-3 expression, Finally, pre-incubation of leukaemic cells with IL-7 increased the proliferation of responding, normal allogenic T lymphocytes and their secretion of gamma-IFN and IL-2 in mixed the lymphocyte-tumour reaction, We concluded that IL-7 is efficient at increasing the membrane expression of molecules which are central for the development of the immune response, and at improving allogenic immune recognition, The clinical implications of su ch data require further in vivo investigation.