Mechanisms of macrophage cytotoxicity in IL-2 and IL-12 mediated tumour regression.
IL-2 and IL-12 are promising anti-tumour agents. However, little attention has been paid to the role of macrophages during IL-2/IL-12 mediated tumour rejection. We studied the role of macrophages during IL-2/IL-12 mediated tumour rejection in DBA/2 mice bearing syngeneic SL2 lymphoma. Local treatment with IL-2 and IL-12 cured 85% of mice with severe metastasised tumour load. In vivo depletion studies showed that macrophages were required for the anti-tumour effect of IL-2 and IL-12. Macrophages could kill tumour cells both non-specifically and by antibody-dependent cellular cytotoxicity (ADCC). Treatment with IL-2, IL-12 or IL-2/IL-12 enhanced production of specific IgG1 immunoglobulins, while treatment with IL-12 and IL-2/IL-12 additionally induced IgG2a production. FcgammaRII and/or III were essential for ADCC expression after treatment with IL-2 and IL-12. These data show for the first time the essential role of macrophages during IL-2/IL-12 mediated tumour rejection and also suggest that IL-2 and IL-12 act via different mechanisms.
Masztalerz
Agnieszka
A
Department of Biochemistry, Cell Biology and Histology, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, The Netherlands. a.masztalerz@vet.uu.nl
Van Rooijen
Nico
N
Den Otter
Willem
W
Everse
Linda A
LA
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000920:Antibody-Dependent Cell Cytotoxicity; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D018664:Interleukin-12 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007700:Kinetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010529:Peritoneal Cavity / Q000166:cytology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D007376:Interleukin-2; D018664:Interleukin-12