Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease

作者：Kondo Tomoyuki; Tsunematsu Takaaki; Yamada Akiko; Arakaki Rieko; Saito Masako; Otsuka Kunihiro; Kujiraoka Satoko; Ushio Aya; Kurosawa Mie; Kudo Yasusei; Ishimaru Naozumi^*

来源：Laboratory Investigation, 2016, 96(4): 468-480.

DOI：10.1038/labinvest.2015.166

Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor-overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1 alpha in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth.

• 出版日期2016-4