<i>Lactobacillus intestinalis</i> facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis
Yong Sun, Qiwen Wang, Yao Jiang, Jiamin He, Dingjiacheng Jia, Man Luo, Wentao Shen, Qingyi Wang, Yadong Qi, Yifeng Lin, Ying Zhang, Lan Wang, Lan Wang, Liangjing Wang, Liangjing Wang, Shujie Chen, Lina Fan
Abstract
Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.