2017年8月29日
Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages
Proceedings of the National Academy of Sciences
- 巻
- 114
- 号
- 35
- 開始ページ
- E7331
- 終了ページ
- E7340
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.1708598114
- 出版者・発行元
- Proceedings of the National Academy of Sciences
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 <italic>basic leucine zipper transcription factor ATF-like 2</italic> (<italic>Batf2</italic>) 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 <italic>Batf2</italic>−/− mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in <italic>Batf2</italic>−/− 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, <italic>Batf2</italic> 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.
- リンク情報
- ID情報
-
- DOI : 10.1073/pnas.1708598114
- ISSN : 0027-8424
- eISSN : 1091-6490
- PubMed ID : 28808017
- PubMed Central 記事ID : PMC5584452