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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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-γ) and third-level chemokines (inducible protein 10 and monokine induced by IFN-γ); (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.

Original languageEnglish
Pages (from-to)414-421
Number of pages8
JournalCancer Research
Volume59
Issue number2
Publication statusPublished - Jan 16 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Immune events associated with the cure of established tumors and spontaneous metastases by local and systemic interleukin 12'. Together they form a unique fingerprint.

Cite this