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The M28 family peptidase (M28), secreted by the commensal bacterium\n                    <jats:italic>Peribacillus frigoritolerans<\/jats:italic>\n                    , acts as a novel inducer of trained immunity with adjuvant potential. In studies using ovalbumin (OVA) as model antigen, both free M28 and M28\u2010loaded liposome (M28\u2010Lipo) significantly enhanced antigen\u2010specific IgG production, stimulated splenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell proliferation, and induced balanced Th1\/Th2 immunity, with M28\u2010Lipo demonstrating superior efficacy. Building on these findings, a biphasic\u2010release breast cancer vaccine (Zfp142\u2010Lipo\u00a0+\u00a0M28@ sodium alginate (ALG)) was developed by co\u2010delivering the tumor\u2010specific neoantigen Zfp142 and M28 using a hydrogel\u2010liposome hybrid system. This formulation enabled sustained antigen release and targeted accumulation in lymph nodes and tumor tissues. Prophylactic administration completely inhibited 4T1 tumorigenesis and pulmonary metastasis, whereas therapeutic administration significantly suppressed tumor progression and dissemination. Mechanistic analysis revealed enhanced infiltration of CD4\u207a and CD8\u207a T cells, reduction of regulatory T cells, and M2\u2010to\u2010M1 macrophage repolarization within the tumor microenvironment. These findings establish M28 as a safe and potent adjuvant that reprograms the tumor microenvironment and effectively bridges innate and adaptive immunity, providing a versatile platform for cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504705","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T05:14:48Z","timestamp":1767071688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Trained Immunity Adjuvant Derived From Commensal Bacteria Potentiates Liposome\u2013Hydrogel Cancer Vaccine Against Breast Tumors"],"prefix":"10.1002","volume":"15","author":[{"given":"Cheng\u2010Kai","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Preventive Veterinary Medicine College of Veterinary Medicine Jilin University  Changchun China"},{"name":"Hospital for Skin Diseases Shandong First Medical University  Jinan 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