{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:07:30Z","timestamp":1791328050910,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T00:00:00Z","timestamp":1237420800000},"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":[[2009,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regulatory T cells (Tregs) play an important role in maintaining immunological tolerance that is one of the main obstacles to overcome for improving antitumor immunity. Recently, the Treg has been shown to constitutively express OX40 (CD134), which is a member of the TNF\u2010receptor family that is transiently expressed on effector T cells after TCR triggering, and through which the signal enhances effector T\u2010cell proliferation and memory T\u2010cell development. However, little is known about the role of OX40 costimulation to Tregs in tumor immunology. Here we show that OX40 signaling modulates the function of naturally occurring Tregs <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Foxp3 expression on Tregs was reduced by OX40 costimulation, but not by IL\u20102 stimulation. Tregs suppressed the proliferation of na\u00efve CD4<jats:sup>+<\/jats:sup> CD25<jats:sup>\u2212<\/jats:sup> T cells after TCR triggering, in contrast, OX40 costimulated Tregs that reduced Foxp3 expression reversed the suppressive function. In addition, Tregs inhibited the proliferation of TCR\u2010stimulated (primed) CD4<jats:sup>+<\/jats:sup> T cells and na\u00efve CD8<jats:sup>+<\/jats:sup> T cells after TCR\u2010mediated activation, however, Tregs with OX40 costimulation lost their suppressive function. Interestingly, Tregs minimally suppressed the proliferation or the cytokine secretion of Ag\u2010specific CD8<jats:sup>+<\/jats:sup> T cells after Ag\u2010restimulation. Furthermore, Tregs suppressive function to the antitumor effect was reversed by OX40 costimulation <jats:italic>in vivo.<\/jats:italic> Our data indicate that, in addition to controlling effector T\u2010cell function, OX40 costimulation directly controls Treg\u2010mediated suppression in tumor immunity. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24435","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T13:18:36Z","timestamp":1237468716000},"page":"630-638","source":"Crossref","is-referenced-by-count":74,"title":["OX40 costimulation can abrogate Foxp3<sup>+<\/sup> regulatory T cell\u2010mediated suppression of antitumor immunity"],"prefix":"10.1002","volume":"125","author":[{"given":"Naomi","family":"Kitamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Ueki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Mekata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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