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Previously, we reported transient growth of poorly immunogenic murine non\u2010Hodgkin B\u2010cell lymphomas (B\u2010NHL) by targeting natural killer T (NKT) cells with a therapeutic vaccine approach. Therapeutic efficacy was highly dependent on the ability of the vaccine to provoke rapid interferon\u2010gamma (IFN\u03b3) production from NKT and NK cells. By manipulating the capacity of either host or lymphoma cells to signal through the IFN\u03b3 receptor (IFN\u03b3R), we investigated whether the therapeutic effect conferred by vaccine\u2010induced IFN\u03b3 is a result of immune cell activation, lymphoma IFN\u03b3 sensitivity or a combination of both. We demonstrated that antitumour immunity elicited by vaccination requires IFN\u03b3 signalling within host cells but not tumour cells. IFN\u03b3R\u2010deficient mice failed to mount an effective antitumour immune response following vaccination despite elevated IFN\u03b3 levels. With successive exposure to vaccination, lymphomas acquired an increasingly therapy\u2010resistant phenotype and displayed a reduction in major histocompatibility complex I and CD1d surface expression, which is independent of tumour intrinsic IFN\u03b3 signalling. Our results suggest that immunotherapy\u2010induced IFN\u03b3 production mainly exerts its therapeutic effect via signalling through host cells, rather than directly to tumour cells in B\u2010NHL. This signifies that intact IFN\u03b3 signalling within patients\u2019 immune compartment rather than tumour cell sensitivity to IFN\u03b3 is more critical for successful treatment. Finally, tumour IFN\u03b3 signalling alone does not drive acquired tumour resistance to vaccination, implying that additional immunoediting pathways are responsible for tumour immune escape.<\/jats:p>","DOI":"10.1038\/icb.2016.9","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T10:41:34Z","timestamp":1453286494000},"page":"554-562","source":"Crossref","is-referenced-by-count":7,"title":["Control of B\u2010cell lymphoma by therapeutic vaccination and acquisition of immune resistance is independent of direct tumour IFN\u2010gamma signalling"],"prefix":"10.1111","volume":"94","author":[{"given":"Rory","family":"Rearden","sequence":"first","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia","family":"Sah","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna","family":"Doff","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara J","family":"McKee","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham R","family":"Leggatt","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen R","family":"Mattarollo","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute  Brisbane Queensland 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