Reversing the polarization of tumor-associated macrophages inhibits tumor metastasis

Publication date: August 2017
Source:International Immunopharmacology, Volume 49
Author(s): Rufei Yuan, Shengfu Li, Hua Geng, Xin Wang, Qinglin Guan, Xiaohuan Li, Changle Ren, Xiaolin Yuan
ObjectiveThe M2 phenotype is dominant in tumor associated macrophages (TAM), and plays a key role in promoting tumor growth, invasion and metastasis. Converting TAM polarization from M2 to M1 may contribute to eliciting anti-tumor-specific immune responses and inhibiting tumor metastasis. In this study, the effect of reversing the polarization of TAM on tumor metastasis was investigated.MethodsPeritoneal macrophages were obtained from BABL/c mice, and M2 polarization was induced by IL-4. In an in vivo experiment, BABL/c mice were transplanted with 4T1 tumor cells. In vitro and in vivo experimental studies, M2 macrophage polarization was reversed with CpG-DNA or CpG-DNA combined with anti-IL-10R Ab. CD68, MHCII and FRβ molecular expression in macrophages were examined with immunofluorescence staining. The mRNA expression of IL-2, IL-6, IL-13, VEGF and MMP-9 were detected with RT-PCR. VEGF and MMP-9 protein expression of tumors in situ was measured by western blot assay. Lung-metastasis of the tumor was observed and assessed by micro-CT.ResultsCpG-DNA and CpG-DNA combined with anti-IL-10R Ab could promote MHCII, IL-2, IL-6 and IL-13 molecular expression, and suppress the expression of FRβ, MMP-9 and VEGF, in both freshly isolated peritoneal macrophages and M2 macrophages. In the CpG-DNA combined with anti-IL-10R Ab injecting group, the percentage of CD68⁺ MHCII⁺ cells were significantly higher than that of CD68⁺FRβ⁺ cells (P<0.05). This was distinct from the result of the control group, which CD68⁺ FRβ⁺ was higher than CD68⁺MHCII⁺cells (P<0.01). Furthermore, VEGF-A and MMP-9 level in primary tumor tissues in the experimental group was significantly lower (P<0.01), compared to the control group. Moreover, the number of detectable lung-metastasis foci was significantly lower in the experimental group than in the control group (P<0.05).ConclusionReversing the polarization of TAM from M2 to M1 phenotype can inhibit tumor metastasis.

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