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[Cancer Research 59, 414-421, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 414-421, January 15, 1999]
© 1999 American Association for Cancer Research

Immunology

Immune Events Associated with the Cure of Established Tumors and Spontaneous Metastases by Local and Systemic Interleukin 121

Federica Cavallo, Emma Di Carlo, Monia Butera, Roberta Verrua, Mario P. Colombo, Piero Musiani and Guido Forni2

Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano [F. C., M. B., R. V., G. F.]; Department of Oncology and Neurosciences, University of Chieti, 66100 Chieti [E. D. C., P. M.]; and National Tumor Institute, 20133 Milan [M. P. C.], Italy

The antitumor activity of recombinant murine interleukin-12 (rIL-12) is documented by a large set of data from numerous mouse models. Because the cellular and molecular mechanisms by which rIL-12 impairs tumor growth are still not fully defined, we compared the effects of local and systemic rIL-12 administration in mice harboring an invasive 7-day-old moderately differentiated and spontaneously metastasizing mammary adenocarcinoma (TSA). Whereas the immune events elicited via the two routes of rIL-12 administration seem to be the same, systemic rIL-12 is markedly more effective; tumor destruction is dependent on a prompt antitumor response resulting from the cooperation of several subsets of reactive cells. The reactions that seem to play a key role are: (a) indirect inhibition of angiogenesis by secondary cytokines (mainly IFN-{gamma}) and third-level chemokines (inducible protein 10 and monokine induced by IFN-{gamma}); (b) systemic activation of leukocyte subsets capable of producing proinflammatory cytokines, CTLs, and antitumor antibodies; and (c) destruction of tumor vessels by polymorphonuclear cells. The markedly higher efficacy of systemic rIL-12 seems to rest on its ability to recruit these systemic reactions more quickly and efficiently than local rIL-12.




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Copyright © 1999 by the American Association for Cancer Research.