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SJTU Research Team Discovered Critical Tumor Immune Suppressor

July 23, 2019      Author: SJTU College of Basic Medical Sciences

Recently, a research team led by Professor Cheng Jinke from College of Basic Medical Sciences, SJTU recently published their research result on the Cancer Research (Influence factor: 20.56), a well-known journal in the field of Cancer Research. Entitled SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development and Function, their study identified SENP1, an essential tumor immune suppressor, discovered its influence on MDSC development and function, and proved its potential value in clinical cancer treatment.

Doctoral student Huang Xian, Master student Wang Xiuzhi, and Associate Professor Zuo Yong are the first authors of the paper. Associate Professor Zuo Yong and Professor Cheng Jinke from College of Basic Medical Sciences, SJTU are the co-corresponding authors. Funded by the National Natural Science Foundation of China, the research was also supported by the College of Basic Medical Sciences of SJTU.

Abstract

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 immune-suppressive 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 de-conjugate SUMOylated CD45. In Senp1-/- MDSC, CD45 was highly SUMOylated, which reduced its phosphatase activity towardSTAT3, 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.

Translated by ZHU Fengyan   Reviewed by WANG Bingyu