{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:27:18Z","timestamp":1787329638500,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"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":["82273359"],"award-info":[{"award-number":["82273359"]}],"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":["82473022"],"award-info":[{"award-number":["82473022"]}],"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":["82003163"],"award-info":[{"award-number":["82003163"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The efficacy of chemotherapy in colorectal cancer (CRC) is closely linked to its ability to remodel the tumor immune microenvironment (TIME), though the underlying molecular determinants remain incompletely defined. Here, we identified tumor\u2010cell intrinsic autophagy as a pivotal orchestrator of an immunologically active TIME, essential for chemotherapy response. We demonstrated that 5\u2010FU\/Oxaliplatin treatment triggers autophagy\u2010dependent TIMP\u20102 production, which restrains MMP\u20102\/9 activity and promotes intra\u2010tumoral accumulation of active CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Disruption of this axis\u2014through autophagy deficiency or loss of TIMP\u20102\u2014leads to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell exclusion and therapeutic resistance. Conversely, restoration of TIMP\u20102 or co\u2010administration of MMP\u20102\/9 inhibitor successfully reinvigorated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the tumor and revived treatment efficacy. Mechanistically, autophagy\u2010mediated degradation of FBXW2 leads to the accumulation of C\/EBP\u03b2 via the ubiquitin\u2010proteasome pathway, thereby driving transcriptional upregulation of TIMP\u20102. Clinically, autophagy status and TIMP\u20102 expression correlated with favorable immune profiles and improved clinical outcomes. These findings establish the autophagy\u2013TIMP\u20102 axis as a key determinant of chemotherapy\u2010induced immune remodeling and a potential target for enhancing therapeutic response and patient stratification in CRC.\n                  <\/jats:p>","DOI":"10.1002\/advs.77349","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:25:03Z","timestamp":1787325903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autophagy Orchestrates Anti\u2010Tumor Immunity to Enhance Chemosensitivity via the FBXW2\/C\/EBP\u03b2\/TIMP\u20102 Axis in Colorectal Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-7739","authenticated-orcid":false,"given":"Bing","family":"Cheng","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoying","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitong","family":"Niu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojie","family":"Long","sequence":"additional","affiliation":[{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Department of General Surgery, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhen","family":"Weng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiufeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9667-3303","authenticated-orcid":false,"given":"Ronghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pharmacy college Jinan University  Guangzhou China"},{"name":"Cancer Research Institute Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore Agency for Science, Technology, and Research (A*STAR)  Biopolis Singapore"},{"name":"Department of Physiology, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Cancer and Stem Cell Biology Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojian","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Department of General Surgery, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8947-4867","authenticated-orcid":false,"given":"Wenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21731"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00586"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201019933\u20100"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201023\u20100857"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010023\u201000585\u2010z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v7.i11.271"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.721624"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100227\u2010y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2249762"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113808"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100367\u20109"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100368\u20108"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00408"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201022\u20104001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2319901"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033946\u2010x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050136\u2010z"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102229\u20105"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100661\u2010y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801348115"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102022\u2010328845"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.02.008"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90895"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425\u2010017\u20100235\u20104"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI156821"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009015\u20101"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.039"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100127"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2047384"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2023-331342"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010025\u201002185\u20109"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2025.2469315"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110075"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.MCR\u201018\u20100024"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2019.1639303"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.115"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107867"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.30.21362"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.045"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306176200"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010020\u201000780\u2010z"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.01.029"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00031.2016"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1207016"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009289\u20105"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010021\u201000862\u20104"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201006127\u2010x"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010019\u20101380\u20100"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.13312"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421\u2010021\u201000312\u2010y"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.13.25"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1046652"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/mog2.89"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201052977\u20100"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010025\u201006566\u20104"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.218169"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.013"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201046606\u2010z"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2025.2481001"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.048"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.12.007"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010023\u201001314\u20106"},{"issue":"11","key":"e_1_2_9_65_1","article-title":"CDK5 destabilizes PD\u2010L1 via Chaperon\u2010mediated Autophagy to Control Cancer Immune Surveillance in Hepatocellular Carcinoma","volume":"11","author":"Ruonan Z.","year":"2023","journal-title":"Journal for ImmunoTherapy of Cancer"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1100785"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201024687\u20104"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77349","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77349","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:25:05Z","timestamp":1787325905000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":66,"alternative-id":["10.1002\/advs.77349"],"URL":"https:\/\/doi.org\/10.1002\/advs.77349","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2026-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77349"}}