| First Author | Huang X | Year | 2019 |
| Journal | Cancer Res | Volume | 79 |
| Issue | 15 | Pages | 3891-3902 |
| PubMed ID | 31186231 | Mgi Jnum | J:278170 |
| Mgi Id | MGI:6342579 | Doi | 10.1158/0008-5472.CAN-18-3497 |
| Citation | Huang X, et al. (2019) SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development and Function. Cancer Res 79(15):3891-3902 |
| abstractText | Myeloid-derived suppressor cells (MDSC) can suppress immunity and promote tumorigenesis, and their abundance is associated with poor prognosis. In this study, we show that SUMO1/sentrin-specific peptidase 1 (SENP1) regulates the development and function of MDSC. SENP1 deficiency in myeloid cells promoted MDSC expansion in bone marrow, spleen, and other organs. Senp1(-/-) MDSC showed stronger immunosuppressive activity than Senp1(+/+) MDSC; we observed no defects in the differentiation of myeloid precursor cell in Senp1(-/-) mice. Mechanistically, SENP1-mediated regulation of MDSC was dependent on STAT3 signaling. We identified CD45 as a specific STAT3 phosphatase in MDSC. CD45 was SUMOylated in MDSC and SENP1 could deconjugate SUMOylated CD45. In Senp1(-/-) MDSC, CD45 was highly SUMOylated, which reduced its phosphatase activity toward STAT3, leading to STAT3-mediated MDSC development and function. These results reveal a suppressive function of SENP1 in modulating MDSC expansion and function via CD45-STAT3 signaling axis. SIGNIFICANCE: These findings show that increased SUMOylation of CD45 via loss of SENP1 suppresses CD45-mediated dephosphorylation of STAT3, which promotes MDSC development and function, leading to tumorigenesis. |
