{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:19:04Z","timestamp":1785403144721,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Huikang Charity Foundation","award":["LH2022H021"],"award-info":[{"award-number":["LH2022H021"]}]},{"DOI":"10.13039\/100020440","name":"Beijing Health Promotion Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020440","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0566ftd35","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) remains an incurable hematological malignancy in which tumor-intrinsic immune evasion limits the efficacy of immunotherapy. Here, we identify the RNA editing enzyme ADAR1 as a key regulator of innate immune suppression in MM. Integrative analyses of bulk and single-cell transcriptomic datasets, together with clinical validation, demonstrated that ADAR1 is upregulated in malignant plasma cells and is associated with adverse clinical outcomes and reduced CD8+ T-cell infiltration. Mechanistically, ADAR1 knockdown increased the association of endogenous dsRNA with melanoma differentiation-associated protein 5 (MDA5), restoring type I interferon (IFN) signaling, enhancing IFN\u03b1 production and STAT1 activation, and promoting CD8+ T-cell proliferation and cytotoxic function. These effects were largely abolished by MDA5 depletion, establishing a functional ADAR1\u2013MDA5 signaling axis in MM. In vivo, treatment with 8-azaadenosine significantly potentiated the antitumor efficacy of PD-1 blockade, resulting in reduced tumor growth, increased tumor cell apoptosis, elevated IFN\u03b1 expression, and enhanced CD8+ T-cell infiltration. Together, our findings demonstrate that ADAR1-mediated RNA editing enables immune evasion by restricting MDA5-dependent sensing of endogenous dsRNA and highlight the ADAR1\u2013MDA5-type I interferon axis as a promising therapeutic target for improving immunotherapy in multiple myeloma.<\/jats:p>","DOI":"10.3390\/ijms27156602","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:53:26Z","timestamp":1784901206000},"page":"6602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting ADAR1 Restores Interferon Signaling and Enhances Immunotherapy Response in Multiple Myeloma"],"prefix":"10.3390","volume":"27","author":[{"given":"Songze","family":"Leng","sequence":"first","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China"},{"name":"Department of Cell Biology, School of Basic Medicine, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyao","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China"},{"name":"Department of Cell Biology, School of Basic Medicine, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China"},{"name":"Department of Cell Biology, School of Basic Medicine, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-1496","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China"},{"name":"Department of Cell Biology, School of Basic Medicine, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1001\/jama.2022.0003","article-title":"Diagnosis and Management of Multiple Myeloma: A Review","volume":"327","author":"Cowan","year":"2022","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/oncolo\/oyad306","article-title":"Perspectives on the Treatment of Multiple Myeloma","volume":"29","author":"Rafae","year":"2024","journal-title":"Oncologist"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s43556-024-00188-w","article-title":"Multiple myeloma: Signaling pathways and targeted therapy","volume":"5","author":"Lu","year":"2024","journal-title":"Mol. 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