American Association for Cancer Research
00085472can183497-sup-211673_3_supp_5533689_ps96sr.pdf (977.58 kB)

Supplementary Figure 6 from SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development and Function

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journal contribution
posted on 2023-03-31, 02:25 authored by Xian Huang, Yong Zuo, Xiuzhi Wang, Xuefeng Wu, Hongsheng Tan, Qiuju Fan, Baijun Dong, Wei Xue, Guo-Qiang Chen, Jinke Cheng

CD45 but not PTP1B is involved in expansion of Senp1-/- MDSC


National Natural Science Foundation of China

Natural Science Foundation of Shanghai

Shanghai Committee of Science and Technology

Shanghai Municipal Commission of Health

Shanghai Municipal Education Commmission



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. 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.