Acute myeloid leukaemia triggering via CD40 induces leukocyte chemoattraction and cytotoxicity against allogenic or autologous leukemic targets

The CD40 antigen is a member of the tumor necrosis factor receptor superfam ily which interacts with its ligand and regulates the immune response via a dialogue between T-lymphocytes and antigen-presenting or tumor cells. Tumo r triggering via CD40 exerts direct effects on cancer cells, which have mai nly been investigated in terminally differentiated hematological malignanci es such as low-grade lymphoma. We focused our attention on minimally differ entiated acute myeloid leukemia (AML-M0), an aggressive hematological malig nancy in which severe prognosis suggests the requirement for innovative the rapeutic strategies. Here we demonstrate, for the first time to our knowled ge, a CD40-triggered IL-8, RANTES and IL-12 secretion by leukemic cells. Su pernatants from CD40-stimulated leukemia cells had chemoattractant effects on T-lymphocytes, natural killer cells and monocytes, Moreover, these super natants, when complemented with low-dose IL-2, induced significant lymphoki ne-activated and natural killer cytotoxicity, leading to leukemia lysis bot h in allogenic HLA-matched and autologous settings. Stimulation of leukemia cells via CD40 could participate significantly to the anti-leukemia immune response by contributing to the development of an inflammatory response an d to in situ cytotoxicity.