Arginase-1 and Ym1 Are Markers for Murine, but Not Human, Alternatively Activated Myeloid Cells

Raes, Geert; Bergh, Rafaël Van den; Baetseĺier, Patrick De; Ghassabeh, Gholamreza Hassanzadeh

doi:10.4049/jimmunol.174.11.6561

Cited by 262 publications

(228 citation statements)

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“…Arginase inhibition might not be as effective in humans because upregulation of arginase activity has not been observed in human TAMs (49). Given that restoration of MHC-II expression by the HDAC inhibitor VPA suppressed tumor growth in F1-DcR3 mice, epigenetic regulation modifying TAM differentiation may be another important tumor-promoting mechanism that can targeted.…”

Section: Discussionmentioning

confidence: 99%

Decoy Receptor 3 Enhances Tumor Progression via Induction of Tumor-Associated Macrophages

Tai

Chang²,

Lan

et al. 2012

The Journal of Immunology

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Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues. Decoy receptor 3 (DcR3), a member of the TNFR superfamily, is overexpressed in tumor cells and is capable of modulating host immunity as either a neutralizing decoy receptor or an effector molecule. Upregulation of DcR3 has been observed to correlate with a poor prognosis in various cancers. However, the mechanisms underlying the DcR3-mediated tumor-promoting effect remain unclear. We previously demonstrated that DcR3 modulates macrophage activation toward an M2-like phenotype in vitro and that DcR3 downregulates MHC class II expression in TAMs via epigenetic control. To investigate whether DcR3 promotes tumor growth, CT26-DcR3 stable transfectants were established. Compared with the vector control clone, DcR3-transfectants grew faster and resulted in TAM infiltration. We further generated CD68 promoter-driven DcR3 transgenic (Tg) mice to investigate tumor growth in vivo. Compared with wild-type mice, macrophages isolated from DcR3-Tg mice displayed higher levels of IL-10, IL-1ra, Ym1, and arginase activity, whereas the expression of IL-12, TNF-α, IL-6, NO, and MHC class II was downregulated. Significantly enhanced tumor growth and spreading were observed in DcR3-Tg mice, and the enhanced tumor growth was abolished by arginase inhibitor N-ω-hydroxy-l-norarginine and histone deacetylase inhibitor sodium valproate. These results indicated that induction of TAMs is an important mechanism for DcR3-mediated tumor progression. Our findings also suggest that targeting DcR3 might help in the development of novel treatment strategies for tumors with high DcR3 expression.

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Section: Discussionmentioning

confidence: 99%

Decoy Receptor 3 Enhances Tumor Progression via Induction of Tumor-Associated Macrophages

Tai

Chang²,

Lan

et al. 2012

The Journal of Immunology

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“…For instance, the induction of Arg1 expression by IL-4 is only observed in murine macrophages. 38 In yet other cases, the IL-4-regulated genes lack homologs in the other species. For example, Chi3l3 and Chi3l4 (also known as Ym1 and Ym2 respectively) are well-characterized markers of IL-4-activated macrophages in mice; however, they do not have direct homologs in humans.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Alternative activation of tumor-associated macrophages by IL-4

2010

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“…Murine macrophages are well characterized with distinct markers that delineate polarization states in mice such as arginase-1 and Ym1 in M2 polarized states [9]. However human polarized macrophages are poorly characterized.…”

Section: Introductionmentioning

confidence: 99%