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EV070/#348  Galectin-3 facilitates immunosuppression in cervical cancer by regulating MDSCs
  1. Qiuwen Mai,
  2. Qiqiao Du and
  3. Junxiu Liu
  1. The First Affiliated Hospital, Sun Yat-sen University, Department of Obstetrics and Gynecology, Guangzhou City, China

Abstract

Introduction Tumor immune microenvironment plays an important role in tumor development. Myeloid-derived suppressor cells (MDSCs) is recognized as a key mediator of immunosuppression in various cancers. Galectin-3 (Gal-3) secreted by tumor is one of the main molecular mechanisms of tumor immune escape, but its role in cervical cancer (CC) has been little studied.

Methods Immunofluorescent staining and immunofluorescence were used to determine expression of Gal-3 and MDSCs in CC tissue. Prognosis analysis have been executed to define the predicting prognosis value of Gal-3 and MDSCs. Western blot, secretin factors screening, ELISA and flow cytometry have been utilized to further explore the molecular mechanism. In vivo, MDSCs inhibitors was conducted in subcutaneous tumor-bearing mice.

Results Gal-3, a beta-galactoside-binding lectin, had upregulated in CC and was significantly correlated with lymph node metastasis, recurrence and survival. Correlation analysis showed that the expression of Gal3 was correlated with the aggregation of MDSCs. Patients with high abundance of MDSCs have a poor prognosis. Gain and loss-of-function approaches showed that Gal-3 improved the expansion, migration and invasion of M-MDSCs and PMN-MDSCs. Mechanistically, Gal-3 promoted the recruitment of MDSCs by activating STAT3/AKT signaling pathway. Besides, MDSCs inhibited T cells function via secreting IL-6/CXCL2. More importantly, knockdown/overexpression of Gal-3 decrease/increased MDSCs in subcutaneous tumor and bone marrow in vivo. Furthermore, MDSCs inhibitors diminished subcutaneous tumor in vivo.

Conclusion/Implications Our findings reveal a novel molecular mechanism that Gal-3 facilitates immunosuppression in CC by regulating MDSCs and suggest that Gal-3 and MDSCs are novel prognostic factors and potential therapeutic targets in CC.

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