Chemotherapy-mediated induction of PD-L1 via SEI1 facilitates myeloma immune evasion

ABSTRACT: Multiple myeloma (MM) is a malignant neoplasm originating in the plasma cell system, with a higher incidence in elderly individuals. While immune checkpoint blockade-based tumor immunotherapy has shown promising advancements in myeloma treatment, conventional chemotherapy remains the primary therapeutic modality. It remains unclear whether chemotherapy influences the expression of immune checkpoints in myeloma, thus impacting the therapeutic efficacy of checkpoint-related antibodies. In this study, we found that treatment of myeloma cells with chemotherapy drugs such as melphalan or bortezomib induces DNA damage and activates the cGAS/STING signaling pathway. This activation promotes the phosphorylation of the transcription factor IRF7, which then binds to the promoter region of SEI1 gene to enhance its transcription. The SEI1 protein directly interacts with the enhancer factors CBP/p300 and RNA polymerase II (pol II)-associated PAF1 complex, promoting transcriptional activity and leading to the upregulation of PD-L1 expression and causing immune escape in myeloma. These findings not only provide valuable insights for enhancing the therapeutic efficacy of chemotherapy in myeloma but also reveal a novel regulatory mechanism for PD-L1.

INSTRUMENT(S): 6410 Triple Quadrupole LC/MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: rui chen  

LAB HEAD: Chen Rui

PROVIDER: PXD052783 | Pride | 2025-05-26

REPOSITORIES: Pride