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Strategies that integrate potent tumor killing with immunosuppressive microenvironment reprogramming are crucial for the treatment of MPE. Studies show that irradiated tumor cell\u2010derived microparticles (RT\u2010MPs) possess natural tumor\u2010targeting cytotoxicity and innate immune activation properties. To further boost the tumoricidal effects of RT\u2010MPs, we developed innovative chemoradiotherapy\u2010integrated tumor cell\u2010derived microparticles (CR\u2010MPs) by loading RT\u2010MPs with chemotherapeutic agents, including methotrexate (MTX), monomethyl auristatin E (MMAE), or doxorubicin (DOX). CR\u2010MPs exhibited superior tumoricidal activity over both RT\u2010MPs and free drugs against a range of tumors. Specifically, MTX\u2010loaded CR\u2010MPs (CR\u2010MPs@MTX) triggered mitochondrial oxidative stress and immunogenic ferroptosis in tumor cells, while directly reprogramming macrophages toward the M1 phenotype and stimulating dendritic cells via cGAS\u2010STING\/NF\u2010\u03baB pathway activation. In murine MPE models, CR\u2010MPs effectively suppressed tumor progression, extended survival, and demonstrated favorable biosafety.\u00a0When combined with immunotherapy, this approach achieved a cure rate of up to 70%, induced durable immunological memory, and retained efficacy against chemotherapy\u2010resistant tumors. This study establishes CR\u2010MPs as a novel platform with robust therapeutic efficacy against MPE, highlighting their translational potential as a precision concurrent chemoradiotherapy strategy for MPE management in clinical settings.<\/jats:p>","DOI":"10.1002\/jev2.70277","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:09:10Z","timestamp":1775560150000},"source":"Crossref","is-referenced-by-count":1,"title":["Chemoradiotherapy\u2010Integrated Tumor Cell\u2010Derived Microparticles Mediate Tumor Eradication in Malignant Pleural Effusion"],"prefix":"10.1002","volume":"15","author":[{"given":"Minqi","family":"Zhou","sequence":"first","affiliation":[{"name":"Cancer Center Tongji Medical College Union Hospital Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Radiation Oncology Tongji Medical College Union Hospital Huazhong University of Science and Technology Wuhan China"},{"name":"Hubei Key Laboratory of 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