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Mechanisms of macrophage cytotoxicity in IL-2 and IL-12 mediated tumour regression

Agnieszka Masztalerz1, Nico Van Rooijen, Willem Den Otter

  • 1Department of Biochemistry, Cell Biology and Histology, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, The Netherlands. a.masztalerz@vet.uu.nl

Cancer Immunology, Immunotherapy : CII
|April 2, 2003
PubMed

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.

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