Mignot, Gregoire and Ullrich, Evelyn and Bonmort, Mathieu and Menard, Cedric and Apetoh, Lionel and Taieb, Julien and Bosisio, Daniela and Sozzani, Silvano and Ferrantini, Maria and Schmitz, Juerg and Mack, Matthias and Ryffel, Bernard and Bulfone-Paus, Silvia and Zitvogel, Laurence and Chaput, Nathalie (2008) The critical role of IL-15 in the antitumor effects mediated by the combination therapy imatinib and IL-2. JOURNAL OF IMMUNOLOGY, 180 (10). pp. 6477-6483. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)Abstract
The synergistic antitumor effects of the combination therapy imatinib mesylate (IM) and IL-2 depended upon NK1.1-expressing cells and were associated with the accumulation of CD11c(int)B220(+)NK1.1(+) IFN-producing killer dendritic cells (IKDC) into tumor beds. In this study, we show that the antitumor efficacy of the combination therapy was compromised in IL-15 and IFN-type IR loss-of-function mice. IL-15R alpha was required for the proliferation of IKDC during IM plus IL-2 therapy. Trans-presentation of IL-15/IL-15R alpha activated IKDC to express CCR2 and to respond to type 1 IFN by producing CCL2. Moreover, the antitumor effects of the combination therapy correlated with a CCL2-dependent recruitment of IKDC, but not B220(-) NK cells, into tumor beds. Altogether, the IL-15-driven peripheral expansion and the CCL-2-dependent intratumoral chemoattraction of IKDC are two critical parameters dictating the antitumor efficacy of IM plus IL-2 in mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELLS; INNATE IMMUNE-RESPONSES; MURINE DENDRITIC CELLS; REGULATORY T-CELLS; TUMOR-CELLS; NK-CELLS; ADAPTIVE IMMUNITY; CROSS-TALK; I IFN; IMMUNOTHERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Nov 2020 06:07 |
| Last Modified: | 03 Nov 2020 06:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30901 |
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