Natural Killer Cell IFNγ Secretion is Profoundly Suppressed Following Colorectal Cancer Surgery

Abstract

Surgical stress results in a significant reduction in natural killer (NK) cell cytotoxicity (NKC), which has been linked to postoperative cancer metastases. However, few studies have measured the impact of surgical stress upon NK cell IFNγ secretion (NKA), a cytokine with essential roles in controlling infection and metastases. The objective of this study was to investigate the impact of surgical stress on NKA in colorectal cancer (CRC) surgery patients. Peripheral blood was collected from CRC surgery patients ( n = 42) preoperatively and on postoperative day (POD) 1, 3, 5, 28, and 56. Healthy donor blood ( n = 27) was collected for controls. We assessed NKA by production of IFNγ following whole blood cytokine stimulation, NKC by 51 Cr-release assay, and immune cell profiling by flow cytometry. The mean reduction in NKA on POD1 compared with baseline was 83.1% (standard deviation 25.2%; confidence interval 75–91), and therefore the study met the primary endpoint of demonstrating a > 75% decrease in a cohort of CRC surgery patients ( p < 0.0001). The profound and universal suppression of NKA persisted with 65.5% (19/29) and 33.3% (4/12) of patients with levels measuring < 75% of baseline on POD28 and POD56 respectively. The NKC was significantly reduced on POD1, but the degree was less pronounced (24.6%, p = 0.0024). Immune cell profiling did not reveal differences in the absolute number of NK cells (CD3 − CD56 + ) or the ratio of CD56 dim -to-CD56 bright subsets. NKA is significantly suppressed for up to two months following surgery in CRC patients, a degree of surgery-induced immunosuppression far worse than previously reported.