{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:21:51Z","timestamp":1781108511115,"version":"3.54.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"14","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1300602"],"award-info":[{"award-number":["2021YFA1300602"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472775"],"award-info":[{"award-number":["82472775"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403202"],"award-info":[{"award-number":["82403202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"GDSTC | Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515012624"],"award-info":[{"award-number":["2025A1515012624"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:p>\n                    Deciphering the mechanisms underlying antitumor immunity is critical for improving cancer immunotherapy efficacy. Here, we identify WFDC21P (lnc-DC) as a positive regulator of antitumor immunity through promoting the activation of the RNA-sensing retinoic acid-inducible gene-I (RIG-I) pathway in triple-negative breast cancer (TNBC). WFDC21P directly binds to RIG-I-interacting protein G3BP1 and is required for a rapid assembly of functional G3BP1-RIG-I-double-stranded RNAs condensates via phase separation, which enables robust activation of RIG-I. WFDC21P is downregulated in TNBC tissues and correlates with less CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration in tumors and worse outcome of patients. WFDC21P knockdown in TNBC cells markedly dampens RIG-I activation and reduces the expression of IFN-stimulated genes, including MHC-I and PD-L1. In syngeneic tumor models, WFDC21P expression not only suppresses tumor growth by augmenting the infiltration and cytotoxic function of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells but also improves the response to immune checkpoint blockade, thus providing a compelling combination immunotherapy strategy for treating triple-negative breast cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2532576123","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:01:31Z","timestamp":1774980091000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["WFDC21P is essential for G3BP1-mediated RIG-I activation and antitumor immunity in triple-negative breast cancer"],"prefix":"10.1073","volume":"123","author":[{"given":"Zean","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9580-0235","authenticated-orcid":false,"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Hao","family":"Lai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Na","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6435-7303","authenticated-orcid":false,"given":"Man-Li","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]},{"name":"Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00430-1"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01405-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.12.012"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.041"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00462-5"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.008"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2281"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3845"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00672-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0400-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.046"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a032813"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02791-14"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2178-9"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3612"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0302-5"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz430"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz008"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt006"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-311"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0816"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac969"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.031"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1020"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-0761"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.7"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4382"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.035"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800129"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00848-3"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-018-0108-y"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251456"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03297-2"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04021-y"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1158-y"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf6548"},{"key":"e_1_3_4_37_2","unstructured":"Z. Li . Effect of WFDC21P knockdown in BT549 cells. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE303355. Deposited 22 July 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2532576123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:01:57Z","timestamp":1774980117000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2532576123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":37,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,4,7]]}},"alternative-id":["10.1073\/pnas.2532576123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2532576123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"2025-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2532576123"}}