Int Immunopharmacol. 2025 Apr 29;157:114693. doi: 10.1016/j.intimp.2025.114693. Online ahead of print.
ABSTRACT
Myeloid-derived suppressor cells (MDSCs) encompass monocytes and granulocytes, which are innate immune cells capable of suppressing T cells and NK cells. MDSCs exert numerous detrimental effects, as they facilitate tumor initiation, promote tumor growth and metastasis, suppress host immune responses, and evade immune surveillance, thereby hindering anticancer responses. Conversely, in autoimmune diseases, MDSCs exhibit dysfunctional immunosuppressive functions and often display pro-inflammatory effects, which can exacerbate immune disorders. We postulate that this discrepancy is attributable to the involvement of the Notch signaling pathway. The Notch signaling pathway is an evolutionarily conserved mechanism that plays a crucial role in maintaining normal mammalian physiological functions. The Notch receptor undergoes three cleavage events before being transported into the nucleus, where it regulates the transcription of target genes. The role of Notch or MDSCs in different diseases has been fully reported, but the regulatory role of Notch signaling pathway on MDSCs in different diseases has been rarely reported.In this review, we characterize the activation, expansion, and immune suppression mechanisms of MDSCs. We then introduce the Notch signaling pathway and finally discuss its role in colorectal cancer, breast cancer, lung cancer, as well as T-cell acute lymphoblastic leukemia, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The Notch signaling pathway regulates MDSCs through distinct mechanisms in these contexts. We hope this review will aid both beginners and experts in systematically understanding the regulation of MDSCs by the Notch signaling pathway in cancer and autoimmune diseases.
PMID:40306114 | DOI:10.1016/j.intimp.2025.114693