RRC ID 66048
著者 Kanemaru H, Yamane F, Fukushima K, Matsuki T, Kawasaki T, Ebina I, Kuniyoshi K, Tanaka H, Maruyama K, Maeda K, Satoh T, Akira S.
タイトル Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages.
ジャーナル Proc Natl Acad Sci U S A
Abstract 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.
巻・号 114(35)
ページ E7331-E7340
公開日 2017-8-29
DOI 10.1073/pnas.1708598114
PII 1708598114
PMID 28808017
PMC PMC5584452
MeSH Animals Antineoplastic Agents / metabolism Basic-Leucine Zipper Transcription Factors / genetics Basic-Leucine Zipper Transcription Factors / metabolism Basic-Leucine Zipper Transcription Factors / pharmacology Basic-Leucine Zipper Transcription Factors / physiology* CD8-Positive T-Lymphocytes / metabolism Gene Expression Regulation / genetics Humans Interleukin-12 / metabolism Interleukin-12 / physiology Macrophages / metabolism Membrane Glycoproteins / metabolism Mice Mice, Transgenic NF-kappa B / metabolism Protein Subunits / metabolism RAW 264.7 Cells Toll-Like Receptor 7 / metabolism Transcription Factors / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / pharmacology Tumor Suppressor Proteins / physiology* Up-Regulation
IF 9.412
リソース情報
ヒト・動物細胞 Colon-26(RCB2657) B16F10(RCB2630) LLC(RCB0558)