Phagocytes as Trojan horse for Fusobacterium nucleatum routing to the tumor tissues and enhance tumor metastasis
The facultative intracellular bacterium Fusobacterium nucleatum (Fn), mediates tumorigenesis and progression in CRC. However, the origin of intracellular Fn and the role of Fn-infected phagocytes in tumor microenvironment remains unclear. Here, we observed Fn-infected neutrophils/macrophages (PMNs/MF) is accumulated in CRC tumor tissues. Fn can survive inside of PMNs by reducing intracellular ROS levels. The lysozyme inhibitor Fn-MliC induced the expression of the CX3CR1 which suppressed apoptosis of phagocytes. Fn-infected phagocytes can transfer Fn to tumor cells, and Fn-infected CRC cells recruited PMNs and MF/monocytes through the CXCL2/8-CXCR2 and CCL5/CCR5 axis. Intracellular Fn upregulated PD-L1 expression through activating NF-?B/STAT3 pathway in PMNs. PD-L1+ PMNs infiltration promotes CRC metastasis and weaken the efficacy of immunotherapy, and eradication intracellular Fn infection retarded the Fn promoted tumor progressing in mice. These results suggest that Fn volved efficient strategies to exploit phagocytes to home to tumor tissues, inhibited immune responses and facilitate tumor metastasis. Overall design: To explore the mechanism of Fn-MliC-attenuated apoptosis,we performed transcriptome profiling experiments in Fn-MliC-treated mouse leukocytes