Intestinal obstruction impairs the antitumor function of hepatic natural killer cells against colorectal cancer.

Abstract

BACKGROUND: This study aimed to investigate the impact of intestinal obstruction (IO) caused by colorectal cancer (CRC) on the cancer prognosis and recurrence patterns. We analyzed recurrence patterns in patients with stage II-III CRC and employed a murine model to elucidate the effects of IO on hepatic immunity. METHODS: We examined the clinical outcomes of CRC patients with IO and utilized a murine IO model to assess alterations in hepatic immunity, focusing on natural killer (NK) cell function. RESULTS: IO was significantly associated with poor prognosis and an increased incidence of liver metastases. In the murine model, IO induced hepatic inflammation and impaired the antitumor activity of liver-resident NK cells, whereas its effects on conventional splenic and pulmonary NK cells were minimal. These findings, consistent between human clinical data and murine experiments, suggest that IO promotes a microenvironment conducive to liver metastasis by compromising hepatic immunity. CONCLUSIONS: IO exerts a detrimental effect on hepatic immunity by impairing NK cell-mediated antitumor responses, thereby facilitating liver metastasis in CRC.