Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

Biochem Biophys Res Commun. 2015 Feb 13;457(3):445-50. doi: 10.1016/j.bbrc.2015.01.011. Epub 2015 Jan 13.


Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit potent immunosuppressive activity. They are increased in tumor-bearing hosts and contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate the tumor-supporting properties of MDSCs through pattern-recognition. Pam2 lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor function by dendritic cell (DC)-priming that leads to NK cell activation and cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell progression/invasion by activating tumor-infiltrating macrophages. How MDSCs respond to TLR2 agonists has not yet been determined. In this study, we found intravenous administration of Pam2CSK4 systemically up-regulated the frequency of MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was accordingly increased in response to Pam2CSK4. MDSCs were not increased by Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor-bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC population sustained immune-suppressive properties, our study suggests that Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress antitumor immune response in tumor microenvironment.

Keywords: Antitumor immunotherapy; Immunosuppression; Myeloid-derive suppressor cells (MDSCs); Pam2 lipopeptides; Toll-like receptor 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Immunotherapy
  • Ligands
  • Lipopeptides / immunology
  • Lipopeptides / metabolism
  • Lipopeptides / pharmacology*
  • Lymphoma / immunology
  • Lymphoma / metabolism
  • Lymphoma / therapy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism*
  • Signal Transduction / drug effects
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Tumor Microenvironment


  • Ligands
  • Lipopeptides
  • Pam2CSK4 lipopeptide
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2