Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages

作者：Kanemaru Hisashi; Yamane Fumihiro; Fukushima Kiyoharu; Matsuki Takanori; Kawasaki Takahiro; Ebina Isao; Kuniyoshi Kanako; Tanaka Hiroki; Maruyama Kenta; Maeda Kazuhiko; Satoh Takashi; Akira Shizuo^*

来源：Proceedings of the National Academy of Sciences, 2017, 114(35): E7331-E7340.

DOI：10.1073/pnas.1708598114

• Batf2
• macrophage
• IL-12 p40
• NF-kappa B
• TLR7

The development of effective treatments against cancers is urgently needed, and the accumulation of CD8(+) T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40(+) macrophages and activated CD8(+) T cells within the tumors of Batf2(-/-) mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in Batf2(-/-) macrophages following their stimulation by toll-like receptor ligands, such as R848. Additionally, we found that BATF2 interacts with p50/p65 and promotes IL-12 p40 expression. In conclusion, Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces CD8(+) T-cell activation and accumulation within the tumor.

• 出版日期2017-8-29