Original Research ARTICLE
S100A4 protects myeloid-derived suppressor cells from intrinsic apoptosis via TLR4-ERK1/2 signaling
- 1Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Institute of Biophysics (CAS), China
- 2First Affiliated Hospital of Zhengzhou University, China
Myeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse tumor models with MDSC accumulation. Spontaneous rejection of tumors implanted into mice deficient for the small Ca2+-binding protein S100A4 (S100A4−/−) was accompanied by low numbers of peripheral MDSCs. This was independent of S100A4 expression on tumor cells. In contrast, MDSCs from S100A4−/− tumor bearing mice showed a diminished resistance to the induction of intrinsic apoptosis. Further studies demonstrated that S100A4 protects MDSCs from apoptosis through Toll-like receptor-4/extracellular signal-regulated kinase-dependent caspase-9 inhibition. The finding that S100A4 is critical for MDSC survival in inflammatory environments might have important implications for the clinical treatment of cancer or inflammation-related diseases.
Keywords: S100A4, MDSCs, intrinsic apoptosis, TLR4, ERK1/2 signaling
Received: 18 Dec 2017;
Accepted: 12 Feb 2018.
Edited by:Giovanna Schiavoni, Istituto Superiore di Sanità, Italy
Reviewed by:Justin Lathia, Cleveland Clinic Lerner College of Medicine, United States
Carlos Alfaro, Universidad de Navarra, Spain
Copyright: © 2018 Li, Dai, Xue, Wang, Han, Erben and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Zhihai Qin, Institute of Biophysics (CAS), Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Beijing, China, firstname.lastname@example.org