某种肠道细菌
结直肠癌
癌症研究
癌变
免疫系统
TLR2型
生物
发病机制
肿瘤微环境
癌症
免疫学
医学
先天免疫系统
内科学
肠道菌群
作者
Lina Fan,Chaochao Xu,Qi-Wei Ge,Yi-Feng Lin,Chi-Huey Wong,Yadong Qi,Bin Ye,Qing-Wu Lian,Wei Zhuo,Jianmin Si,Shujie Chen,Liangjing Wang
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2021-08-13
卷期号:9 (10): 1111-1124
被引量:35
标识
DOI:10.1158/2326-6066.cir-20-1019
摘要
The interplay between gut microbiota and the host immune system is emerging as a factor in the pathogenesis of colorectal cancer. Here, we set out to identify the effect of Akkermansia muciniphila (A. muciniphila) on colorectal cancer pathogenesis. A. muciniphila abundance was significantly reduced in patients with colorectal cancer from two independent clinical cohorts and the GMrepo dataset. Supplementation with A. muciniphila suppressed colonic tumorigenesis in ApcMin/+ mice and the growth of implanted HCT116 or CT26 tumors in nude mice. Mechanistically, A. muciniphila facilitated enrichment of M1-like macrophages in an NLRP3-dependent manner in vivo and in vitro. As a consequence, NLRP3 deficiency in macrophages attenuated the tumor-suppressive effect of A. muciniphila. In addition, we revealed that TLR2 was essential for the activation of the NF-κB/NLRP3 pathway and A. muciniphila induced M1-like macrophage response. We observed positive correlations between M1-like macrophages, NLRP3/TLR2 and A. muciniphila in patients with colorectal cancer, which corroborated these findings. In summary, A. muciniphila-induced M1-like macrophages provide a therapeutic target in the colorectal cancer tumor microenvironment.
科研通智能强力驱动
Strongly Powered by AbleSci AI