Characterization of systemic neutrophil function in patients undergoing colorectal cancer resection

BACKGROUND: In patients with colorectal cancer, the generation and maintenance of a systemic inflammatory response is associated with poor outcomes. Neutrophils have been implicated in the prognosis of such patients, but little is known about their functional response to surgery. This study was conducted to characterize neutrophil function of patients undergoing colorectal cancer resection.

MATERIALS AND METHODS: Systemic neutrophils were isolated from patients with colorectal cancer who underwent surgical resection preoperatively (day 0) and postoperatively (day 1 and day 3). Neutrophils were stimulated to produce neutrophil extracellular traps, which were quantified by a measure of the fluorescence of the extracellular DNA. Neutrophil apoptosis and phagocytosis were measured by fluorescence-activated cell sorting.

RESULTS: Forty-five patients were evaluated. Statistically significant differences were identified in NET formation over the perioperative period (reduced NET production [day 0 to day 1] and restored NET production [day 1 to day 3]) in the absence of stimulation (P = 0.0016) and in response to stimulation with interleukin 8 (P = 0.0045), lipopolysaccharide (P = 0.0025), and N-formylmethionyl-leucyl-phenylalanine (P = 0.0014). No statistically significant differences were identified in apoptosis at 4-hour incubation; however, at 24-hours, significant differences were identified in alive (P < 0.0001), early apoptotic (P = 0.0008) and late apoptotic (P = 0.0018) stages (impaired apoptosis [day 0 to day 1] and restored apoptosis [day 1 to day 3]). Demonstrable, but nonsignificant, increases in neutrophil phagocytotic activity were revealed on sequential perioperative days, and a significant increase in phagocytosis was identified from day 1 to day 3 in response to E coli (P = 0.0078).

CONCLUSIONS: A novel neutrophil phenotype demonstrating reduced NET formation, reduced apoptosis, and increased phagocytosis has been demonstrated in patients undergoing colorectal cancer resection. As a consequence of impaired cell death, an accumulation of neutrophils in the circulation could be potentially harmful to the host following surgery and an early phenotypic switch may be desirable.