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Publication : Immune events associated with the cure of established tumors and spontaneous metastases by local and systemic interleukin 12.

First Author  Cavallo F Year  1999
Journal  Cancer Res Volume  59
Issue  2 Pages  414-21
PubMed ID  9927056 Mgi Jnum  J:52037
Mgi Id  MGI:1327728 Citation  Cavallo F, et al. (1999) Immune events associated with the cure of established tumors and spontaneous metastases by local and systemic interleukin 12. Cancer Res 59(2):414-21
abstractText  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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