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Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as\n                    <jats:italic>Mycobacterium brumae<\/jats:italic>\n                    , and\/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and\/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of\n                    <jats:italic>ex vivo<\/jats:italic>\n                    splenocytes cultured with mycobacteria antigens. In both BCG- and\n                    <jats:italic>M. brumae<\/jats:italic>\n                    -treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-33253-w","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T09:42:52Z","timestamp":1538646172000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-0673","authenticated-orcid":false,"given":"Estela","family":"Noguera-Ortega","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9521-791X","authenticated-orcid":false,"given":"Rosa M.","family":"Rabanal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"G\u00f3mez-Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9941-6828","authenticated-orcid":false,"given":"Cecilia","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Luquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-3978","authenticated-orcid":false,"given":"Esther","family":"Juli\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"33253_CR1","unstructured":"Ferlay, J. et al. 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E.N.-O., M.L. and E.J. are the inventors of the patent application, PCT\/EP2014\/062941, \u201cOil-in-water formulations of Mycobacterium and uses thereof\u201d The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15102"}}