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 superfamily which interacts with its ligand and regulates the immune response via a dialogue between T-lymphocytes and antigen-presenting or tumor cells. Tumor triggering via CD40 exerts direct effects on cancer cells, which have mainly been investigated in terminally differentiated hematological malignancies such as low-grade lymphoma. We focused our attention on minimally differentiated acute myeloid leukemia (AML-M0), an aggressive hematological malignancy in which severe prognosis suggests the requirement for innovative therapeutic strategies. Here we demonstrate, for the first time to our knowledge, a CD40-triggered IL-8, RANTES and IL-12 secretion by leukemic cells. Supernatants from CD40-stimulated leukemia cells had chemoattractant effects on T-lymphocytes, natural killer cells and monocytes. Moreover, these supernatants, when complemented with low-dose IL-2, induced significant lymphokine-activated and natural killer cytotoxicity, leading to leukemia lysis both 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 and to in situ cytotoxicity. Leukemia(2000) 14, 123-128.
Costello
R T
RT
Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France.
Mallet
F
F
Chambost
H
H
Sainty
D
D
Arnoulet
C
C
Gastaut
J A
JA
Olive
D
D
D000208:Acute Disease; D019013:CD40 Antigens / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D002630:Chemotactic Factors; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*
D019013:CD40 Antigens; D018925:Chemokines; D002630:Chemotactic Factors; D018664:Interleukin-12