Ampicillin-resistant Klebsiella pneumoniae enhances neutrophil infiltration to induce liver metastasis of colorectal cancer_scRNA-Seq

The emergence of research on intratumoral bacteria and its correlation with the post-metastatic niche has garnered interest, yet the impact on liver metastasis of colorectal cancer through neutrophils remains unexplored. Our study confirmed the enrichment of ampicillin-resistant Klebsiella pneumoniae (Am-R-Kp) in the niche post-liver metastasis, revealing that Am-R-Kp bolstered infiltration by activating RIPK2 phosphorylation of neutrophils. This activation induced heightened expression of S100A8/9-ERK-STAT3 in colorectal cancer cells, resulting in increased invasion, migration, and proliferation. However, the precise mechanism remains unclear. Our recent findings indicated that RIPK2 enhanced the expression of ATF3/RelB and S100A8/9 interacted with STAT3. As a result, we hypothesized that ATF3/RelB binds to the promoter and enhancer regions of specific genes in neutrophils, leading to their chemotactic and survival effects. Additionally, in cancer cells, S100A8/9 binding to STAT3 facilitated the proximity of promoters and enhancers of downstream genes through the common motifs. This study offered a theoretical foundation supporting the assertion that "intratumoral bacteria facilitate the liver metastasis of colorectal cancer," and contributed to the advancement of immunotherapy medications designed to target Am-R-Kp and RIPK2.