Peroxisome Proliferator-activated Receptor Gamma (Ppargamma) Ligands Reverse Ctl Suppression by Alternatively Activated (M2) Macrophages in Cancer.
From: Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Brussels, Belgium. jvangind@vub.ac.be
Blood
- Publish Date: Jul 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 2
- Pages: 525-35
- Medium: Print
- Language: English
- Citation (JAMA): Van Ginderachter Jo A, Meerschaut Sofie, Liu Yuanqing, et al. Peroxisome Proliferator-activated Receptor Gamma (Ppargamma) Ligands Reverse Ctl Suppression by Alternatively Activated (M2) Macrophages in Cancer.. Blood Jul 2006;108:525-35
Abstract
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 into a CD11b(hi)Gr-1(int)SSC(lo)Ly6G(neg)M-CSFR(int) immature monocytic fraction and a CD11b(hi+)Gr-1(hi)SSC(hi)Ly6G(hi)M-CSFR(neg) granulocytic fraction. Upon in vitro culture, the monocytic CD11b(+)Gr-1(+) cell fraction is sufficient for cytotoxic T lymphocyte (CTL) suppression, which is linked to the gradual differentiation of these monocytic cells 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 gamma (PPARgamma) and inhibition of phospholipase A(2) (PLA(2)) activity cooperate to alleviate CTL suppression. Of importance, purified tumor-associated macrophages display a similar M2 phenotype and are suppressive for antitumor CTLs, via a mechanism that can be almost completely reversed by PPARgamma ligands. Overall, our data identify PLA(2) and especially PPARgamma as new potential therapeutic targets to subvert macrophage-mediated CTL suppression in cancer.
Mesh Headings (Keywords): Animals, Cell Differentiation, Cells, Cultured, Ligands, Lymphoma, T-Cell, Macrophages, Mice, Monocytes, Neoplasms, PPAR gamma, Phospholipases A, Spleen, T-Lymphocytes, Cytotoxic, Tumor Escape
Check for Full Text / PubMed Unique Identifier (PMID): 16527895
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