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Blood, 15 July 2006, Vol. 108, No. 2, pp. 525-535. Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-09-3777. This Article Full Text (PDF) All Versions of this Article: 2005-09-3777v1 108/2/525    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Ginderachter, J. A Articles by De Baetselier, P. Search for Related Content PubMed PubMed Citation Articles by Van Ginderachter, J. A Articles by De Baetselier, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 20, 2005 Accepted February 27, 2006 Peroxisome proliferator-activated receptor (PPAR) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer Jo A Van Ginderachter*, Sofie Meerschaut, Yuanqing Liu, Lea Brys, Kurt De Groeve, Gholamreza Hassanzadeh Ghassabeh, Geert Raes, and Patrick De Baetselier Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Brussels, Belgium * Corresponding author; email: jvangind{at}vub.ac.be. Tumors may escape from immune control by the induction of CD11b+Gr-1+ myeloid suppressor cells in the spleen. In this study, we demonstrate that this cell population can be subdivided in a CD11bhi Gr-1int SSClo Ly6Gneg M-CSFRint immature monocytic fraction and a CD11bhi+ Gr-1hi SSChi Ly6Ghi M-CSFRneg granulocytic fraction. Upon in vitro culture, the monocytic CD11b+Gr-1+ cell fraction is sufficient for CTL suppression, linked to their gradual differentiation into mature F4/80+ CD68+ macrophages. These CTL-suppressive macrophages are alternatively activated (M2), as demonstrated by the expression of known and novel M2 signature genes. In search of M2-associated genes involved in the suppressive activity, it is shown that stimulation of peroxisome proliferator-activated receptor (PPAR) and inhibition of phospholipase A2 (PLA2) activity co-operate to alleviate CTL suppression. Importantly, purified tumor-associated macrophages display a similar M2 phenotype and are suppressive for anti-tumor CTLs, via a mechanism which can be almost completely reversed by PPAR ligands. Overall, our data identify PLA2 and especially PPAR as new potential therapeutic targets to subvert macrophage-mediated CTL suppression in cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Van den Bossche, P. Bogaert, J. van Hengel, C. J. Guerin, G. Berx, K. Movahedi, R. Van den Bergh, A. Pereira-Fernandes, J. M. C. Geuns, H. Pircher, et al. Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes Blood, November 19, 2009; 114(21): 4664 - 4674. [Abstract] [Full Text] [PDF] D. Ruffell, F. Mourkioti, A. Gambardella, P. Kirstetter, R. G. Lopez, N. Rosenthal, and C. Nerlov A CREB-C/EBP{beta} cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair PNAS, October 13, 2009; 106(41): 17475 - 17480. [Abstract] [Full Text] [PDF] A. P. Lepique, K. R. P. Daghastanli, I. M. Cuccovia, and L. L. Villa HPV16 Tumor Associated Macrophages Suppress Antitumor T Cell Responses Clin. Cancer Res., July 1, 2009; 15(13): 4391 - 4400. [Abstract] [Full Text] [PDF] E. Eruslanov, S. Kaliberov, I. Daurkin, L. Kaliberova, D. Buchsbaum, J. Vieweg, and S. Kusmartsev Altered Expression of 15-Hydroxyprostaglandin Dehydrogenase in Tumor-Infiltrated CD11b Myeloid Cells: A Mechanism for Immune Evasion in Cancer J. Immunol., June 15, 2009; 182(12): 7548 - 7557. [Abstract] [Full Text] [PDF] K. Movahedi, M. Guilliams, J. Van den Bossche, R. Van den Bergh, C. Gysemans, A. Beschin, P. De Baetselier, and J. A. Van Ginderachter Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity Blood, April 15, 2008; 111(8): 4233 - 4244. [Abstract] [Full Text] [PDF] S. Z. Duan, M. G. Usher, and R. M. Mortensen Peroxisome Proliferator-Activated Receptor-{gamma}-Mediated Effects in the Vasculature Circ. Res., February 15, 2008; 102(3): 283 - 294. [Abstract] [Full Text] [PDF] G. Caljon, J. Van Den Abbeele, B. Stijlemans, M. Coosemans, P. De Baetselier, and S. Magez Tsetse Fly Saliva Accelerates the Onset of Trypanosoma brucei Infection in a Mouse Model Associated with a Reduced Host Inflammatory Response Infect. Immun., November 1, 2006; 74(11): 6324 - 6330. [Abstract] [Full Text] [PDF]

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