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Adjuvant\u2010induced trained innate immune responses constitute a critical yet underexplored component of adjuvant mechanisms of action. Here, KK2DP7, a dendrimer\u2010structured peptide derived from the immunomodulatory antimicrobial peptide DP7 (VQWRIRVAVIRK) is employed, as a model adjuvant to establish standardized protocols for investigating adjuvant efficacy and mechanisms in enhancing anti\u2010tumor immunity via trained immunity. Initial studies revealed that KK2DP7 administration significantly delayed tumor growth post\u2010inoculation in murine models. The comprehensive analysis demonstrated that splenic cells exhibited cardinal features of trained immunity, whereas splenectomized mice exhibited complete loss of this protective effect. Strikingly, the adoptive transfer of CD11b\n                    <jats:sup>+<\/jats:sup>\n                    cells isolated from the non\u2010lymphoid splenic compartment of KK2DP7\u2010trained mice to na\u00efve recipients conferred robust tumor suppression. Mechanistic investigations linked this phenomenon to TLR2\u2010IRF7 axis activation and epigenetic reprogramming of CD11b\n                    <jats:sup>+<\/jats:sup>\n                    cells, as evidenced by chromatin accessibility assays and histone modification profiling. These findings not only unveil a novel therapeutically actionable dimension of trained immunity, centered on spleen\u2010resident CD11b\n                    <jats:sup>+<\/jats:sup>\n                    cell reprogramming but also establish a standardized protocol framework for systematically investigating adjuvant mechanisms in the context of trained innate immunity.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500032","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T04:56:23Z","timestamp":1743310583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["KK2DP7 Stimulates CD11b\n                    <sup>+<\/sup>\n                    Cell Populations in the Spleen to Elicit Trained Immunity for Anti\u2010Tumor Therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu 610041 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00845-6"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00633-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.10.011"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260127"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.058"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.059"},{"key":"e_1_2_9_5_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01388-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100107"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-339812"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131335"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242841"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564497"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2022.106361"},{"key":"e_1_2_9_8_3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202870109"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.12.008"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.622614"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-69781-x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300116"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02823-14"},{"key":"e_1_2_9_10_3","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00368-18"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01428-x"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.030"},{"key":"e_1_2_9_11_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.034"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03047"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03086"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00791-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13022"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.119852"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.21"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.101"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.89"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MR0717-292R"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.12.005"},{"key":"e_1_2_9_18_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.047"},{"key":"e_1_2_9_18_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.11.008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004485"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv332"},{"key":"e_1_2_9_20_1","volume":"19","author":"Liu 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