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

Abstract

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. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential formore » Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.« less

Authors:
; ; ; ; ;
Publication Date:
OSTI Identifier:
22458481
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 457; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BUILDUP; CELL PROLIFERATION; CYSTEINE; DAMAGE; DENDRITES; IMMUNOSUPPRESSION; IMMUNOTHERAPY; IN VIVO; LYMPHOCYTES; MACROPHAGES; MICE; NATURAL KILLER CELLS; NEOPLASMS; PATTERN RECOGNITION; RECEPTORS; SIGNALS; STIMULI; TUMOR CELLS

Citation Formats

Maruyama, Akira, Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp, Takeda, Yohei, Azuma, Masahiro, Matsumoto, Misako, and Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp. Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.01.011.
Maruyama, Akira, Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp, Takeda, Yohei, Azuma, Masahiro, Matsumoto, Misako, & Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp. Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling. United States. doi:10.1016/J.BBRC.2015.01.011.
Maruyama, Akira, Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp, Takeda, Yohei, Azuma, Masahiro, Matsumoto, Misako, and Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp. Fri . "Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling". United States. doi:10.1016/J.BBRC.2015.01.011.
@article{osti_22458481,
title = {Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling},
author = {Maruyama, Akira and Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp and Takeda, Yohei and Azuma, Masahiro and Matsumoto, Misako and Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp},
abstractNote = {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. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential for Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.},
doi = {10.1016/J.BBRC.2015.01.011},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 457,
place = {United States},
year = {Fri Feb 13 00:00:00 EST 2015},
month = {Fri Feb 13 00:00:00 EST 2015}
}