{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:55:39Z","timestamp":1787741739889,"version":"build-2784847793"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T00:00:00Z","timestamp":1261958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>IL\u201021 is a member of the IL\u20102 cytokine family, produced by CD4+ T cells. We previously showed that immunotherapy (IT) with IL\u201021\u2010transduced neuroblastoma cells (Neuro2a\/IL\u201021) cured 33% of syngeneic mice bearing systemic NB. Here, we studied whether the removal of Treg cells could potentiate the therapeutic efficacy of Neuro2a\/IL\u201021 vaccine. The administration of anti\u2010CD25 mAb, which targets Treg cells, slightly potentiated the effect of vaccine IT (50% cure rate), but anti\u2010CD4 mAb had a more potent effect leading to 80% cure rate. Anti\u2010CD25 mAb, indeed, only partially depleted CD4+CD25+FoxP3+ Treg cells, whereas anti\u2010CD4 mAb was more effective in this respect, leading to 90% depletion of Treg cells. In mice receiving vaccine+anti\u2010CD4 mAb, which developed systemic immunity to NB, CD4+ T cells counts completely recovered in 90 days. Depletion of CD8+ T cells abrogated the effect of the combined IT, indicating a predominant role of these cells in driving the immune response. In addition, CD8+ T cells from cured mice coinjected with Neuro2a\/parental cells (pc) in NOD\u2010SCID mice completely inhibited tumor growth. Spleen cells from mice receiving Neuro2a\/IL\u201021 vaccination showed increased expression of IFN\u2010alpha2, \u2010beta1 and \u2010gamma mRNA. Moreover, mice receiving vaccine therapy alone or vaccine+anti\u2010CD4 mAb showed increased IFN\u2010gamma serum levels and IFN\u2010gamma\u2010producing CD8+ T cells were found in spleen cells. In conclusion, anti\u2010CD4 mAb potentiated IL\u201021\u2010based IT by removing Treg cells and\/or their precursors and other potentially immune\u2010suppressive CD4+ cell subsets, thus allowing the development of an IL\u201021\u2010driven CD8+ T cell response, which mediates NB rejection.<\/jats:p>","DOI":"10.1002\/ijc.25140","type":"journal-article","created":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T15:11:22Z","timestamp":1262013082000},"page":"1141-1150","source":"Crossref","is-referenced-by-count":24,"title":["Transient depletion of CD4<sup>+<\/sup> T cells augments IL\u201021\u2010based immunotherapy of disseminated neuroblastoma in syngeneic mice"],"prefix":"10.1002","volume":"127","author":[{"given":"Michela","family":"Croce","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Valeria","family":"Corrias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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