{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:35:41Z","timestamp":1764138941986,"version":"3.46.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Intravesical treatment with\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    Ty21a, an oral typhoid-fever vaccine, has shown therapeutic potential against bladder tumors mainly through local immune-cell recruitment, particularly CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells. However, the mechanisms underlying its efficacy and the impact of bacterial formulation remain unclear. Here, we show that increased immune-cell infiltration was neither associated with modification in blood vessel density nor the generation of high endothelial venules, but rather with a transient increase in local vessel permeability, requiring live bacteria. Giving prior evidence that freshly harvested bacteria (Ty21a\n                    <jats:sup>FR<\/jats:sup>\n                    ) were more efficient than lyophilized bacteria (Ty21a\n                    <jats:sup>LYO<\/jats:sup>\n                    ), we tested both formulations intravesically in mice. Although, both similarly increased vascular permeability, Ty21a\n                    <jats:sup>FR<\/jats:sup>\n                    induced significantly greater immune-cell recruitment locally and more effective tumor regression in the orthotopic MB49 bladder cancer model. Chemokine analysis showed higher levels of C5a, CXCL2 and CXCL5 in Ty21a\n                    <jats:sup>FR<\/jats:sup>\n                    -treated bladders, however their receptors (C5aR, CXCR2) were barely detected on infiltrating T cells, precluding their direct involvement in T-cell recruitment. Instead, Ty21a\n                    <jats:sup>FR<\/jats:sup>\n                    increased C5aR\n                    <jats:sup>+<\/jats:sup>\n                    and C5aR\n                    <jats:sup>-<\/jats:sup>\n                    CD11b\n                    <jats:sup>high<\/jats:sup>\n                    myeloid cells, suggesting their indirect influence on T-cell recruitment. We hypothesized that LPS, a TLR4 agonist, from\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , might be involved. Indeed, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell infiltration following Ty21a\n                    <jats:sup>FR<\/jats:sup>\n                    was significantly decreased in TLR4- and MyD88-KO mice. In contrast, myeloid-cell recruitment was only reduced in MyD88-KO mice, suggesting the involvement of TLR4-independent pathways in that process. This study is the first to identify Ty21a formulation-driven immunostimulatory differences in bladder cancer. Altogether, our data provide new insights into Ty21a\u2019s immunostimulatory mechanisms and highlight the importance of bacterial formulation for optimizing bladder cancer treatment.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1629462","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:31:42Z","timestamp":1764138702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Ty21a immunostimulatory effects in the mouse bladder"],"prefix":"10.3389","volume":"16","author":[{"given":"Lenka","family":"Polak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rim","family":"Hojeij","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Cesson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques-Antoine","family":"Haefliger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Roger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Lucca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Derr\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Nardelli-Haefliger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Domingos-Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.eururo.2020.09.006","article-title":"Global trends of bladder cancer incidence and mortality, and their associations with tobacco use and gross domestic product per capita","volume":"78","author":"Teoh","year":"2020","journal-title":"Eur Urol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17022","DOI":"10.1038\/nrdp.2017.22","article-title":"Bladder cancer","volume":"3","author":"Sanli","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1142","article-title":"Association between smoking and risk of bladder cancer among men and women","volume":"306","author":"Freedman","year":"2011","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-021-00481-1","article-title":"100 years of Bacillus Calmette-Guerin immunotherapy: from cattle to COVID-19","volume":"18","author":"Lobo","year":"2021","journal-title":"Nat Rev Urol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.05.041","article-title":"EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016","volume":"71","author":"Babjuk","year":"2016","journal-title":"Eur Urol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.04.038","article-title":"An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer","volume":"56","author":"Malmstrom","year":"2009","journal-title":"Eur Urol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.11.023","article-title":"The role of bacillus Calmette-Guerin in the treatment of non-muscle-invasive bladder cancer","volume":"57","author":"Gontero","year":"2010","journal-title":"Eur Urol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.11.031","article-title":"Therapeutic options in high-risk non-muscle-invasive bladder cancer during the current worldwide shortage of bacille Calmette-Guerin","volume":"67","author":"Mostafid","year":"2015","journal-title":"Eur Urol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30512-8","article-title":"Bladder cancer","volume":"388","author":"Kamat","year":"2016","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/131.5.553","article-title":"Isolation and characterization of galE mutant Ty 21a of Salmonella typhi. 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