Postoperative Abdominal Infectious Complications Promote Colon Cancer Metastasis by Inducing MDSCs to Release Neutrophil Extracellular Traps.

PURPOSE: Surgical resection is the primary treatment for colon cancer. Postoperative abdominal infectious complications (AIC) are associated with poor prognosis, but their mechanistic role in promoting metastasis remains unclear. This study aimed to investigate the association between AIC and metastasis, focusing on the potential involvement of myeloid-derived suppressor cells (MDSCs) and neutrophil extracellular traps (NETs).

PATIENTS AND

METHODS

Peripheral blood from colon cancer patients with (AIC, n = 20) or without (Non-AIC, n = 20) postoperative abdominal infectious complications was analyzed by flow cytometry to assess MDSC frequency and NET markers. A mouse model of postoperative infection following tumor resection was established. Metastatic burden was evaluated using in vivo imaging and histopathological analysis. MDSC function and NET induction were further examined using in vitro co-culture assays.

RESULTS

In patients, MDSC and NET markers were elevated on postoperative day 3. By day 7, levels remained significantly higher in AIC patients compared to Non-AIC patients. In mice, AIC triggered a systemic expansion of MDSCs in peripheral blood, bone marrow, and ascites, accompanied by increased NET formation. These AIC-induced MDSCs and NETs promoted tumor cell migration and accelerated liver and peritoneal metastasis in vivo. Critically, degrading NETs with DNase I markedly reduced metastatic burden without exacerbating sepsis.

CONCLUSION

Postoperative infection is associated with enhanced colon cancer metastasis, and experimental data indicate that the MDSC-NETs axis is involved in this process. Pharmacological disruption of NETs with DNase I represents a potential therapeutic strategy that warrants further investigation for improving postsurgical outcomes.