TLR2-Mediated Expansion of MDSCs Is Dependent on the Source of Tumor Exosomes

被引:74
作者
Xiang, Xiaoyu [1 ]
Liu, Yuelong [3 ]
Zhuang, Xiaoyin [1 ]
Zhang, Shuangqin [2 ,3 ]
Michalek, Sue [4 ]
Taylor, Douglas D. [1 ]
Grizzle, William [5 ]
Zhang, Huang-Ge [1 ,6 ]
机构
[1] Univ Louisville, Dept Microbiol & Immunol, James Brown Canc Ctr, Louisville, KY 40202 USA
[2] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA
[3] Univ Alabama, Dept Med, Birmingham, AL 35294 USA
[4] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA
[5] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA
[6] Robley Rex Med Ctr, Louisville, KY USA
基金
美国国家卫生研究院;
关键词
SUPPRESSOR-CELLS; INFLAMMATION; PROGRESSION; MICE; CYTOTOXICITY; INDUCTION; CANCER;
D O I
10.2353/ajpath.2010.100245
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Exosomes released from tumor cells having been shown to induce interleukin-6 release from myeloid-derived suppressor cells in a Toll-like receptor 2/Stat3-dependent manner. In this study, we show that exosomes released from tumor cells re-isolated from syngeneic mice are capable of inducing interleukin-6 in a Toll-like receptor 2-independent manner, whereas the data generated from exosomes of tumor cells having undergone numerous in vitro passages induce interleukin-6 in a Toll-like receptor 2-dependent manner. This discrepancy may be due to the source of tumor cells used to generate the exosomes for this study. These results suggest that exosomes released from tumor cells that are not within a tumor microenvironment may not realistically represent the role of tumor exosomes in vivo. This is an important consideration since frequently passing tumor cells in vivo is an accepted practice for studying tumor exosome-mediated inflammatory responses. (Ant J Patbal 2010, 177:1606-1610; DOI: 10.2353/ajpath.2010.100245)
引用
收藏
页码:1606 / 1610
页数:5
相关论文
共 28 条
[1]   Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo [J].
Bhatnagar, Sanchita ;
Shinagawa, Kazuhiko ;
Castellino, Francis J. ;
Schorey, Jeff Rey S. .
BLOOD, 2007, 110 (09) :3234-3244
[2]   Exosomes released from infected macrophages contain mycobacterium avium glycopeptidolipids and are proinflammatory [J].
Bhatnagar, Sanchita ;
Schorey, Jeffrey S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (35) :25779-25789
[3]   Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression [J].
Bunt, SK ;
Sinha, P ;
Clements, VK ;
Leips, J ;
Ostrand-Rosenberg, S .
JOURNAL OF IMMUNOLOGY, 2006, 176 (01) :284-290
[4]   Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression [J].
Bunt, Stephanie K. ;
Yang, Linglin ;
Sinha, Pratima ;
Clements, Virginia K. ;
Leips, Jeff ;
Ostrand-Rosenberg, Suzanne .
CANCER RESEARCH, 2007, 67 (20) :10019-10026
[5]   Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells [J].
Chalmin, Fanny ;
Ladoire, Sylvain ;
Mignot, Gregoire ;
Vincent, Julie ;
Bruchard, Melanie ;
Remy-Martin, Jean-Paul ;
Boireau, Wilfrid ;
Rouleau, Alain ;
Simon, Benoit ;
Lanneau, David ;
De Thonel, Aurelie ;
Multhoff, Gabriele ;
Hamman, Arlette ;
Martin, Francois ;
Chauffert, Bruno ;
Solary, Eric ;
Zitvogel, Laurence ;
Garrido, Carmen ;
Ryffel, Bernhard ;
Borg, Christophe ;
Apetoh, Lionel ;
Rebe, Cedric ;
Ghiringhelli, Francois .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (02) :457-471
[6]   Myeloid-derived suppressor cells as regulators of the immune system [J].
Gabrilovich, Dmitry I. ;
Nagaraj, Srinivas .
NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :162-174
[7]   Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice [J].
Grizzle, William E. ;
Xu, Xin ;
Zhang, Shuangqin ;
Stockard, Cecil R. ;
Liu, Cunren ;
Yu, Shaohua ;
Wang, Jianhua ;
Mountz, John D. ;
Zhang, Huang-Ge .
MECHANISMS OF AGEING AND DEVELOPMENT, 2007, 128 (11-12) :672-680
[8]   TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β [J].
Kagan, Jonathan C. ;
Su, Tian ;
Horng, Tiffany ;
Chow, Amy ;
Akira, Shizuo ;
Medzhitov, Ruslan .
NATURE IMMUNOLOGY, 2008, 9 (04) :361-368
[9]  
KESSENBROCK K, CELL, V141, P52
[10]   Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function [J].
Liu, CR ;
Yu, SH ;
Zinn, K ;
Wang, JH ;
Zhang, LM ;
Jia, YJ ;
Kappes, JC ;
Barnes, S ;
Kimberly, RP ;
Grizzle, WE ;
Zhang, HG .
JOURNAL OF IMMUNOLOGY, 2006, 176 (03) :1375-1385