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In our investigation, we unveil a non-dose-dependent type of behavior regarding\n                    <jats:italic>Salmonella<\/jats:italic>\n                    \u2019s therapeutic impact and reveal the regulatory role of neutrophils in diminishing the efficacy of this. While\n                    <jats:italic>Salmonella<\/jats:italic>\n                    colonization within tumors recruits a substantial neutrophil population, these neutrophils predominantly polarize into the pro-tumor N2 phenotype, elevating PD-L1 expression and fostering an immunosuppressive milieu within the tumor microenvironment. In order to bypass this challenge, we introduce MnO\n                    <jats:sub>2<\/jats:sub>\n                    nanoparticles engineered to activate the STING pathway. Harnessing the STING pathway to stimulate IFN-\u03b2 secretion prompts a shift in neutrophil polarization from the N2 to the N1 phenotype. This strategic repolarization remodels the tumor immune microenvironment, making the infiltration and activation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells possible. Through these orchestrated mechanisms, the combined employment of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    and MnO\n                    <jats:sub>2<\/jats:sub>\n                    attains the synergistic enhancement of anti-tumor efficacy, achieving the complete inhibition of tumor growth within 20 days and an impressive 80% survival rate within 40 days, with no discernible signs of significant adverse effects. Our study not only unveils the crucial in vivo constraints obstructing microbial immune therapy but also sets out an innovative strategy to augment its efficacy. These findings pave the way for advancements in cell-based immunotherapy centered on leveraging the potential of neutrophils.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12951-024-02726-8","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T04:01:38Z","timestamp":1722052898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Repolarizing neutrophils via MnO2 nanoparticle-activated STING pathway enhances Salmonella-mediated tumor immunotherapy"],"prefix":"10.1186","volume":"22","author":[{"given":"Shan","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieru","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"issue":"6","key":"2726_CR1","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/s41587-022-01294-2","volume":"40","author":"AJ Barbier","year":"2022","unstructured":"Barbier AJ, Jiang AY, Zhang P, Wooster R, Anderson DG. 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