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Titolo:
IFN-gamma and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy
Autore:
Wigginton, JM; Gruys, E; Geiselhart, L; Subleski, J; Komschlies, KL; Park, JW; Wiltrout, TA; Nagashima, K; Back, TC; Wiltrout, RH;
Indirizzi:
NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA NCI Frederick MD USA 21702 nol Lab, Ctr Canc Res, Frederick, MD 21702 USA NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 ol Branch, Ctr Canc Res, Bethesda, MD 20892 USA Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA Sci Applicat Int Corp Frederick MD USA upport Program, Frederick, MD USA
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 1, volume: 108, anno: 2001,
pagine: 51 - 62
SICI:
0021-9738(200107)108:1<51:IAFARF>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-MEDIATED CYTOTOXICITY; NATURAL-KILLER-CELLS; MURINE RENAL-CANCER; FAS LIGAND; TUMOR-CELLS; IN-VIVO; STIMULATORY FACTOR; INTERFERON-GAMMA; PHASE-I; INTERLEUKIN-12;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Wiltrout, RH NCI, Expt Immunol Lab, Ctr Canc Res, Bldg 560,Room 31-93, Frederick, MD 21702 USA NCI Bldg 560,Room 31-93 Frederick MD USA 21702 , MD 21702 USA
Citazione:
J.M. Wigginton et al., "IFN-gamma and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy", J CLIN INV, 108(1), 2001, pp. 51-62

Abstract

Systemic administration of IL-12 and intermittent doses of IL-2 induce complete regression of metastatic murine renal carcinoma. Here, we show that overt tumor regression induced by IL-12/pulse IL-2 is preceded by recruitment of CD8(+) T cells, vascular injury disrupted tumor neovascularization, and apoptosis of both endothelial and tumor cells. The IL-12/IL-2 combinationsynergistically enhances cell surface FasL expression on CD8(+) T lymphocytes in vitro and induces Fas and FasL expression within tumors via an IFN-gamma -dependent mechanism in vivo. This therapy also inhibits tumor neovascularization and induces tumor regression by mechanisms that depend critically on endogenous IFN-gamma production and an intact Fas/FasL pathway. The ability of IL-12/pulse IL-2 to induce rapid destruction of rumor-associated endothelial cells and regression of established metastatic tumors is ablated in mice with a dysregulated Fas/FasL pathway. The common, critical role for endogenous IFN-gamma and the Fas/FasL pathway in early antiangiogenic effects and in antitumor responses suggests that early, cytokine-driven innate immune mechanisms and CD8(+) T cell-mediated responses are interdependent. Definition of critical early molecular events engaged by IL-12/IL-2 may provide new perspective into optimal therapeutic engagement of a productive host-antitumor immune response.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 05:58:04