{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:51:51Z","timestamp":1792183911817,"version":"4.4.0"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,7,25]]},"abstract":"<jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with pronounced resistance to conventional therapies. Irreversible electroporation (IRE) is a promising therapy for PDAC; however, its clinical efficacy is limited by a high recurrence rate. Here, using a preclinical PDAC model, we characterized the tumor immune microenvironment following insufficient IRE (iIRE) through single-cell RNA sequencing. We found that iIRE induces a CCR2\n                    <jats:sup>+<\/jats:sup>\n                    tumor-associated macrophage (CCR2\n                    <jats:sup>+<\/jats:sup>\n                    TAM)\u2013mediated immunosuppressive microenvironment in residual tumors. Consequently, we developed a macrophage-based proteolipid vesicle (mPLV) coencapsulating the CCR2 antagonist PF-4136309 (PF) and gemcitabine (GEM), named PF\/GEM@mPLV. Our findings suggest that PF\/GEM@mPLV achieves high drug accumulation within tumors through iIRE-induced inflammation. Reduction of CCR2\n                    <jats:sup>+<\/jats:sup>\n                    TAMs enhances antitumor immunity and improves chemotherapeutic response. PF\/GEM@mPLV markedly inhibits tumor recurrence following iIRE, diminishes hepatic metastases, and prolongs survival in preclinical PDAC models. These findings uncover the role of CCR2\n                    <jats:sup>+<\/jats:sup>\n                    TAMs in iIRE-induced immunosuppression, offering a promising strategy to enhance the clinical potential of IRE in PDAC.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw2937","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T17:58:39Z","timestamp":1753293519000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Targeting tumor-associated CCR2\n                    <sup>+<\/sup>\n                    macrophages to inhibit pancreatic cancer recurrence following irreversible electroporation"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9141-2374","authenticated-orcid":true,"given":"Weichen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3180-6607","authenticated-orcid":true,"given":"Shaoyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2797-6486","authenticated-orcid":true,"given":"Xuexia","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-9111","authenticated-orcid":true,"given":"Xinhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou 311100, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengbo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Zhejiang Hospital, Hangzhou, Zhejiang Province 310013, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6995-139X","authenticated-orcid":true,"given":"Yincheng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-1497","authenticated-orcid":true,"given":"Dandan","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Shanghai Hospital of Traditional Chinese Medicine, Shanghai 201899, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taixia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, Henan Provincial People\u2019s Hospital, School of Medicine, Henan University, Zhengzhou, Henan 450003, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9878-8590","authenticated-orcid":true,"given":"Huixiong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. 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