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While intraperitoneal immunotherapy (IPIT) has been used in clinical investigations to relieve PM, the limited knowledge of peritoneal immunocytes has hindered the development of therapeutic IPIT. Here, a dendritic cell\u2010independent, next\u2010generation IPIT is described that activates peritoneal cavity B (PerC B) cell subsets for intraperitoneal anti\u2010tumor immunity via exogenous antigen presentation. The PerC B\u2010cell\u2010involved IPIT framework consists of an isotropic\u2010porous, cell\u2010fitting, thermogenetics\u2010based CXCL12 generator. Such nanoscale thermal\u2010confined generator can programmatically fine\u2010tune the expression of CXCL12 to recruit disseminated tumor cells (DTCs) through CXCL12\u2010CXCR4 axis while avoiding cytokine storm, subsequently release DTC\u2010derived antigen to trigger PerC B\u2010cell\u2010involved immunity. Notably, antigen\u2010presenting B\u2010cell cluster, expressing the regulatory signaling molecules <jats:italic>Ptpn6<\/jats:italic>, <jats:italic>Ms4a1<\/jats:italic>, and <jats:italic>Cd52<\/jats:italic>, is identified playing the key role in the IPIT via single\u2010cell RNA sequencing. Moreover, such IPIT availably assuages peritoneal effusion and PM in an orthotopic gastric cancer and metastatic model. Overall, this work offers a perspective on PerC B\u2010cell\u2010involved antigen\u2010presenting in intraperitoneal immunity and\u00a0provides a configurable strategy for activating anti\u2010DTC immunity for next\u2010generation IPIT.<\/jats:p>","DOI":"10.1002\/adma.202411731","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T02:39:59Z","timestamp":1737945599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PerC B\u2010Cells Activation via Thermogenetics\u2010Based CXCL12 Generator for Intraperitoneal Immunity Against Metastatic Disseminated Tumor Cells"],"prefix":"10.1002","volume":"37","author":[{"given":"Zhiwei","family":"Yin","sequence":"first","affiliation":[{"name":"Molecular Science and Biomedicine Laboratory (MBL) State Key Laboratory of Chemo\/Biosensing and Chemometrics College of Chemistry and Chemical Engineering College of Environmental Science and Engineering 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