{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:18Z","timestamp":1790618238824,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403645"],"award-info":[{"award-number":["82403645"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503820"],"award-info":[{"award-number":["82503820"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Macromolecular Bioscience"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) exhibits intrinsic resistance to conventional therapeutic regimens. By integrating single\u2010cell and bulk transcriptomic data from CRC cohorts, we demonstrate that proliferative capacity alone constitutes an inadequate prognostic predictor. Instead, an immunosuppressive tumor microenvironment (TME) emerges as the dominant driver of disease progression. Galectin\u20101 (LGALS1), highly upregulated in metastatic CRC, correlates with robust infiltration of regulatory T cells (Tregs) and M2 macrophages to facilitate immune evasion and poor clinical outcomes, thereby serving as a promising therapeutic target for anti\u2010tumor immunotherapy. The stromal barrier mediated by cancer\u2010associated fibroblasts (CAFs) restricts intratumoral penetration of antitumor agents and diminishes therapeutic efficacy. To overcome this physical barrier, we constructed a CAF extracellular vesicle\u2010based co\u2010delivery platform termed CEV@Comb, encapsulating the LGALS1 inhibitor OTX008 and 5\u2010fluorouracil (5\u2010FU). CEV@Comb selectively accumulates in tumors, suppresses growth in vitro and in vivo, and remodels the immunosuppressive TME by boosting M1 macrophages and cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells while reducing intratumoral Tregs. Combination therapy with CEV@Comb and anti\u2011programmed death\u20111 antibody (\u03b1PD\u20101) further amplifies anti\u2010tumor immunity in the Apc\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , Kras\n                    <jats:sup>G12D<\/jats:sup>\n                    , Trp53\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , Smad4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    (AKPS) CRC mouse model. This study identifies LGALS1 as a core immunosuppressive mediator and provides an innovative chemoimmunotherapeutic strategy to improve clinical outcomes for patients with advanced CRC.\n                  <\/jats:p>","DOI":"10.1002\/mabi.70255","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:51:11Z","timestamp":1789847471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting LGALS1 via CAF\u2010Derived Extracellular Vesicles Synergizes With \u03b1PD\u20101 to Reverse Immunosuppression and Sensibilize Chemo\u2010Immunotherapy for Colorectal Cancer"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7895-8069","authenticated-orcid":false,"given":"Sijia","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing 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