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While immune checkpoint blockade immunotherapy has advanced myeloma treatment, chemotherapy remains the primary therapy. How chemotherapy interacts with immune checkpoint expression and impacts immunotherapy efficacy remains unclear.\u00a0Here it is discovered that chemotherapeutic drugs induce DNA damage and activate the cyclic guanosine monophosphate (GMP)\u2013adenosine monophosphate (AMP) synthase (cGAS)\/stimulator of interferon genes (STING) signaling pathway. This activation promotes phosphorylation of the interferon regulatory factor 7 (IRF7), which binds to the promoter region of SERTA\u2010containing domain 1 (\n                    <jats:italic>SERTAD1<\/jats:italic>\n                    , also called\n                    <jats:italic>SEI1<\/jats:italic>\n                    ) gene to enhance its transcription. The SEI1 directly interacts with the enhancer factors CREB\u2010binding protein (CBP)\/p300 and RNA polymerase II (pol II)\u2010associated factor 1 (PAF1) complex, promoting transcriptional activity and leading to upregulation of programmed death ligand\u20101 (PD\u2010L1) and immune escape in myeloma. Both in vitro and in vivo experiments demonstrate that treating myeloma cells with PD\u2010L1 antibodies post\u2010chemotherapy significantly enhances the killing efficiency of activated T cells, compared to sequential treatment with chemotherapy and PD\u2010L1 antibodies. This research not only uncovers a pivotal regulatory mechanism of PD\u2010L1 upregulation but also provides a compelling rationale for the integration of chemotherapy and immunotherapy in myeloma treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202411082","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T03:34:44Z","timestamp":1743219284000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chemotherapy\u2010Mediated Induction of PD\u2010L1 via SEI1 Facilitates Myeloma Immune Evasion"],"prefix":"10.1002","volume":"12","author":[{"given":"Rui","family":"Chen","sequence":"first","affiliation":[{"name":"Cancer Research Center School of Medicine Xiamen University  Xiamen 361102 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongwei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University  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