Abstract 4007: Differential macrophage programming is associated with the aggressiveness of gliomas

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.4007-4007
• Main Authors: Yao, Nai-Wei, Liao, Fang, Chang, Chen, Chen, Joanne Jeou-Yuan
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-4007

Tumor-associated macrophages (TAMs), a major component of immune cells in the tumor microenvironment, have been shown to be associated with enhanced malignancy of gliomas. The polarization of macrophages toward a pro-inflammatory phenotype M1 or an anti-inflammatory phenotype M2 governed by niche factors in the tumor microenvironment may dictate the malignant outcome of gliomas. In this study, we examined the effects of differential programming of TAMs on the development of C6 gliomas in different host microenvironment using SD and Wistar rats. Using multi-parametric MRI measurements, we show that C6 cells implanted into SD rats developed larger tumors as compared to those in Wistar rats (p = 0.0199), which was accompanied with a shorter survival of SD rats (p = 1.06×10-9). The increased tumor growth in SD rats was associated with increased angiogenesis and higher levels of VEGF and VEGFR2 expression. We also observed a significantly increased ratio of M2/M1 in the tumors of SD rats while a decreased ratio of M2/M1 in those of Wistar rats, suggesting that the milieu of C6 gliomas in SD rats favors for the polarization of macrophages toward the pro-tumorigenic M2 phenotype. Most importantly, Induction of M1 polarization by IFNγ treatment greatly reduced tumor burden in SD rats, and induction of M2 polarization by IL-4/IL-10 treatment or blockade of M1 polarization by anti-IL12 treatment significantly promoted tumor growth in Wistar rats. These results demonstrate an important role of TAMs in glioma pathogenesis and the crucial role of microenvironment in dictating the polarization of TAMs into M1 or M2 phenotypes. We conclude that macrophage programming plays an important role in glioma development and that targeting glioma-associated macrophages may serve as a promising therapeutic approach. Citation Format: Nai-Wei Yao, Fang Liao, Chen Chang, Joanne Jeou-Yuan Chen. Differential macrophage programming is associated with the aggressiveness of gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4007. doi:10.1158/1538-7445.AM2017-4007