Unveiling the covert interaction between gut microbiota and neutrophils to drive colorectal cancer metastasis.

The formation of the microenvironment preceding liver metastasis is intricately linked to the intestinal tract. In recent years, mounting evidence has revealed the significant involvement of neutrophil extracellular traps (NETs) in tumor metastasis, particularly in liver metastasis. Disruption of the intestinal barrier can lead to the translocation of bacteria and their metabolites, such as lipopolysaccharide, into the liver. As the primary defense against pathogens, NETs help eliminate gut-derived toxins and shape the liver's inflammatory and immunosuppressive environment. However, this double-edged sword effect can potentially stimulate tumor metastasis by creating a fertile ground for the growth of intestinal tumor cells due to impaired liver tissue and reduced activity of killer immune cells. This comprehensive review systematically describes the influence factors and mechanisms of NETs in colon cancer metastasis and explores their potential as biomarkers and therapeutic targets for liver metastasis.

Shen P ，Cheng P ，Li Y ，Zong G ，Deng R ，Qian C ，Zhao Y ，Wei Z ，Lu Y ... -  《-》

Crosstalk between gut microbiota and metastasis in colorectal cancer: implication of neutrophil extracellular traps.

Wu J ，Dong W ，Pan Y ，Wang J ，Wu M ，Yu Y ... -  《Frontiers in Immunology》

Emerging Role of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Narrative Review.

Zhang Y ，Song J ，Zhang Y ，Li T ，Peng J ，Zhou H ，Zong Z ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Netting Gut Disease: Neutrophil Extracellular Trap in Intestinal Pathology.

Many gut disease etiologies are attributed to the presence of robust inflammatory cell recruitment. The recruitment of neutrophils plays a vital role in inflammatory infiltration. Neutrophils have various antimicrobial effector mechanisms, including phagocytosis, oxidative burst, and degranulation. It is suggested that neutrophils could release neutrophil extracellular traps (NETs) to kill pathogens. However, recent evidence indicates that neutrophil infiltration within the gut is associated with disrupted local immunological microenvironment and impaired epithelial barrier. Growing evidence implies that NETs are involved in the progression of many diseases, including cancer, diabetes, thrombosis, and autoimmune disease. Increased NET formation was found in acute or chronic conditions, including infection, sterile inflammation, cancer, and ischemia/reperfusion injury (IRI). Here, we present a comprehensive review of recent advances in the understanding of NETs, focusing on their effects in gut disease. We also discuss NETs as a potential therapeutic target in gut disease.

Chen K ，Shao LH ，Wang F ，Shen XF ，Xia XF ，Kang X ，Song P ，Wang M ，Lu XF ，Wang C ，Hu QY ，Liu S ，Guan WX ... -  《-》

The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis.

Neutrophil Extracellular Traps (NETs) are net-like structures composed of DNA-histone complexes and proteins released by activated neutrophils. In addition to their key role in the neutrophil innate immune response, NETs are also involved in autoimmune diseases, like systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and in other non-infectious pathological processes, as coagulation disorders, thrombosis, diabetes, atherosclerosis, vasculitis, and cancer. Recently, a large body of evidence indicates that NETs are involved in cancer progression and metastatic dissemination, both in animal models and cancer patients. Interestingly, a close correlation between cancer cell recruitment of neutrophils in the tumor microenvironment (Tumor Associated Neutrophils. TANs) and NET formation has been also observed either in primary tumors and metastatic sites. Moreover, NETs can also catch circulating cancer cells and promote metastasis. Furthermore, it has been reported that wake dormant cancer cells, causing tumor relapse and metastasis. This review will primarily focus on the pro-tumorigenic activity of NETs in tumors highlighting their ability to serve as a potential target for cancer therapy.

Masucci MT ，Minopoli M ，Del Vecchio S ，Carriero MV ... -  《Frontiers in Immunology》