Chemotherapy-Mediated Induction of PD-L1 via SEI1 Facilitates Myeloma Immune Evasion.

ABSTRACT: Multiple myeloma (MM) is a plasma cell-derived malignancy. 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. Here it is discovered that chemotherapeutic drugs induce DNA damage and activate the cyclic guanosine monophosphate (GMP)-adenosine 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-containing domain 1 (SERTAD1, also called SEI1) gene to enhance its transcription. The SEI1 directly interacts with the enhancer factors CREB-binding

SUBMITTER: Chen R 

PROVIDER: S-EPMC12097018 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature