Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7331-E7340. doi: 10.1073/pnas.1708598114. Epub 2017 Aug 14.
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 () 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 mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in 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, 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.
迫切需要开发有效的癌症治疗方法,肿瘤内 CD8 T 细胞的积累对癌症预后尤其重要。尽管其机制在很大程度上仍不清楚,但越来越多的证据表明,先天免疫细胞通过产生各种细胞因子对癌症的进展有重要影响。在这里,我们发现()具有抗肿瘤作用。与 WT 小鼠相比,在 s.c. 接种肿瘤模型中,小鼠肿瘤内产生的 IL-12 p40 巨噬细胞和激活的 CD8 T 细胞较少。体外研究还表明,在受到 TLR 配体(如 R848)刺激后,巨噬细胞中的 IL-12 p40 表达明显降低。此外,我们发现 BATF2 与 p50/p65 相互作用,促进 IL-12 p40 的表达。总之,通过上调肿瘤相关巨噬细胞中的 IL-12 p40,发挥抗肿瘤作用,最终诱导肿瘤内 CD8 T 细胞的激活和积累。