{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:43:00Z","timestamp":1770295380697,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8216010239"],"award-info":[{"award-number":["8216010239"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Promising outcomes have been observed in multiple myeloma (MM) with the use of immunotherapies, specifically chimeric antigen receptor T (CAR\u2010T) cell therapy. However, a portion of MM patients do not respond to CAR\u2010T therapy, and the reasons for this lack of response remain unclear. The objective of this study was to investigate the impact of miR\u201034a on the immunosuppressive polarization of macrophages obtained from MM patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The levels of miR\u201034a and TLR9 (Toll\u2010like receptor 9) were examined in macrophages obtained from both healthy individuals and patients with MM. ELISA was employed to investigate the cytokine profiles of the macrophage samples. Co\u2010culture experiments were conducted to evaluate the immunomodulatory impact of MM\u2010associated macrophages on CAR\u2010T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was an observed suppressed activation of macrophages and CD4<jats:sup>+<\/jats:sup> T lymphocytes in the blood samples of MM patients. Overexpression of miR\u201034a in MM\u2010associated macrophages dampened the TLR9 expression and impaired the inflammatory polarization. In both the co\u2010culture system and an animal model, MM\u2010associated macrophages suppressed the activity and tumoricidal effect of CAR\u2010T cells in a miR\u201034a\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings imply that targeting the macrophage miR\u201034a\/TLR9 axis could potentially alleviate the immunosuppression associated with CAR\u2010T therapy in MM patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7387","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T11:30:47Z","timestamp":1718191847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>miR<\/scp>\u201034a promotes the immunosuppressive function of multiple myeloma\u2010associated macrophages by dampening the <scp>TLR<\/scp>\u20109 signaling"],"prefix":"10.1002","volume":"13","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Disi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ci","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiapeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianshi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-0800","authenticated-orcid":false,"given":"Xun","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Hematology Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan  No.519 Kunzhou Road, Xishan District Kunming Yunnan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00643-3"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.247"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32928"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004309"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0031-0808.20.04145-2"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.09.001"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00947-6"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2021.100468"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504542"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30115-2"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127684"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10184088"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00962-7"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-22-0074"},{"issue":"3","key":"e_1_2_12_16_1","article-title":"Anti\u2010BCMA CAR T\u2010cell therapy: changing the natural history of multiple myeloma","volume":"6","author":"Puertas B","year":"2022","journal-title":"Hema"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101095"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09943-1"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.778409"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.4814"},{"issue":"11","key":"e_1_2_12_21_1","first-page":"2594","article-title":"miR\u201034a: a pluripotent repressor of proliferation, migration and invasion in cells of cancer and other origins","volume":"13","author":"Bader AG","year":"2021","journal-title":"Cancers (Basel)"},{"key":"e_1_2_12_22_1","first-page":"381","article-title":"miR\u201034 and breast cancer metastasis: a prospective therapy and a tumor suppressor","volume":"8","author":"Navarro F","year":"2017","journal-title":"Mol Ther Nucleic Acids"},{"issue":"12","key":"e_1_2_12_23_1","first-page":"2512","article-title":"Specific activation of microRNA34a by vincristine in multiple myeloma","volume":"12","author":"Sampath D","year":"2013","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2014.47"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.07.694"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118209"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1295-1"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0670-5"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.09.008"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000089"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18186-0"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.607362"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583084"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22340"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-220285"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720948115"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-021-00327-3"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abe2606"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0470-3"},{"issue":"12","key":"e_1_2_12_40_1","first-page":"4038","article-title":"Fueling chimeric antigen receptor T cells with cytokines","volume":"10","author":"Jin J","year":"2020","journal-title":"Am J Cancer Res"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.09.006"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0310153"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00705"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-021-00780-y"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.03.018"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37088"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.7387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T12:16:59Z","timestamp":1719577019000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.7387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/cam4.7387"],"URL":"https:\/\/doi.org\/10.1002\/cam4.7387","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2024-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e7387"}}