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IFN regulatory factor (IRF)\u20101 is a transcriptional regulator of IFNs and IFN\u2010inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation. Aim of this study was to explore the role of IRF\u20101 in CTX\u2010induced antitumor effects and related immune activities. This study shows for the first time that IRF\u20101 is important for the antitumor efficacy of CTX in mice. Moreover, experiments in tumor\u2010bearing C57BL\/6 mice showed that <jats:italic>Irf1<\/jats:italic> gene expression in the spleen was transiently increased following CTX administration and correlated with the induction of Th1 cell expansion and of <jats:italic>Il12p40<\/jats:italic> gene expression, which is the main Th1\u2010driving cytokine. At the same time, CTX administration reduced both <jats:italic>Foxp3<\/jats:italic> expression and Treg cell percentages. These effects were abrogated in <jats:italic>Irf1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. Further experiments showed that the gene and\/or protein expression of caspase\u20101, iNOS, IL\u20101\u03b2, IL\u20106 and CXCL10 and the levels of nitric oxide were modulated following CTX in an IRF\u20101\u2010direct\u2010 or \u2010indirect\u2010dependent manner, and highlighted the importance of caspase\u20101 in driving the sterile inflammatory response to CTX. Our data identify IRF\u20101 as important for the antitumor efficacy of CTX and for the regulation of many immunomodulatory activities of CTX, such as Th1 polarization, Treg depletion and inflammation.<\/jats:p>","DOI":"10.1002\/ijc.31083","type":"journal-article","created":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T10:16:10Z","timestamp":1507112170000},"page":"976-987","source":"Crossref","is-referenced-by-count":34,"title":["Role of interferon regulatory factor 1 in governing <scp>T<\/scp>reg depletion, <scp>T<\/scp>h1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide"],"prefix":"10.1002","volume":"142","author":[{"given":"Carla","family":"Buccione","sequence":"first","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Fragale","sequence":"additional","affiliation":[{"name":"Department of Oncology 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