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These cells developed small tumors that were subsequently rejected by 90% of s.c. injected syngeneic mice. Five days after injection, TS\/A-IL-21 tumors showed numerous infiltrating granulocytes, NK cells, and to a lesser extent CD8+ T cells, along with the expression of TNF-\u03b1, IFN-\u03b3, and endothelial adhesion molecules ICAM-1 and VCAM-1. At day 7, CD8+ and CD4+ T cells increased together with IFN-\u03b3, and the CXC chemokines IFN-\u03b3-inducible protein 10, monokine induced by IFN-\u03b3, and IFN-inducible T cell \u03b1-chemoattractant. The TS\/A-IL-21 tumor displayed a disrupted vascular network with abortive sprouting and signs of endothelial cell damage. In vivo depletion experiments by specific Abs showed that rejection of TS\/A-IL-21 cells required CD8+ T lymphocytes and granulocytes. When injected in IFN-\u03b3-deficient mice, TS\/A-IL-21 cells formed tumors that regressed in only 29% of animals, indicating a role for IFN-\u03b3 in IL-21-mediated antitumor response, but also the existence of IFN-\u03b3-independent effects. Most immunocompetent mice rejecting TS\/A-IL-21 cells developed protective immunity against TS\/A-pc (75%) and against the antigenically related C26 colon carcinoma cells (61%), as indicated by rechallenge experiments. A specific CTL response against the gp70-env protein of an endogenous murine retrovirus coexpressed by TS\/A and C26 cells was detected in mice rejecting TS\/A-IL-21 cells. These data suggest that IL-21 represents a suitable adjuvant in inducing specific CTL responses.<\/jats:p>","DOI":"10.4049\/jimmunol.172.3.1540","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:08:36Z","timestamp":1398028116000},"page":"1540-1547","source":"Crossref","is-referenced-by-count":125,"title":["IL-21 Induces Tumor Rejection by Specific CTL and IFN-\u03b3-Dependent CXC Chemokines in Syngeneic Mice"],"prefix":"10.1093","volume":"172","author":[{"given":"Emma","family":"Di Carlo","sequence":"first","affiliation":[{"name":"Dipartimento di Oncologia e Neuroscienze, Universita\u0300 di Chieti , Chieti ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Comes","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per la Ricerca sul Cancro , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Orengo","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per la Ricerca sul Cancro , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Rosso","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per la Ricerca sul Cancro , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Meazza","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Musiani","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia e Neuroscienze, Universita\u0300 di Chieti , Chieti ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario P","family":"Colombo","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Ferrini","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per la Ricerca sul Cancro , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,2,1]]},"reference":[{"key":"2026020211163459200_R1","first-page":"259","volume-title":"Adv. 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