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

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-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth.

内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201606141010.pdf
審査要旨 : LID201606141011.pdf
論文本文 : k2943_fulltext.pdf
著者の申請により要約(2016-06-15公開)に替えて論文全文を公開(2019-06-05)

本論文は, 著者Tomoyuki Kondoの学位論文として提出され, 学位審査・授与の対象となっている。

This is the Author's Accepted Manuscript of the following article: Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease, Tomoyuki Kondo, Takaaki Tsunematsu, Akiko Yamada, Rieko Arakaki, Masako Saito, Kunihiro Otsuka, Satoko Kujiraoka, Aya Ushio, Mie Kurosawa, Yasusei Kudo & Naozumi Ishimaru, Laboratory Investigation 96, 468-480 (2016), which has been published in final form at https://doi.org/10.1038/labinvest.2015.166.