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

Area of Science:

• Immunology
• Oncology
• Surgical Research

Background:

• Surgical stress is known to reduce natural killer (NK) cell cytotoxicity (NKC), potentially promoting cancer metastasis.
• The impact of surgical stress on NK cell IFNγ secretion (NKA), crucial for infection and metastasis control, remains understudied.
• Colorectal cancer (CRC) surgery patients experience significant surgical stress, necessitating investigation into its effects on immune function.

Purpose of the Study:

• To investigate the impact of surgical stress on NK cell IFNγ secretion (NKA) in patients undergoing colorectal cancer (CRC) surgery.
• To quantify the reduction in NKA following CRC surgery and assess its persistence over time.

Main Methods:

• Peripheral blood samples were collected from 42 CRC surgery patients preoperatively and on postoperative days (POD) 1, 3, 5, 28, and 56.
• Healthy donor blood (n=27) served as controls.
• NKA was measured via IFNγ production post-stimulation, NKC via 51Cr-release assay, and immune cell profiling by flow cytometry.

Main Results:

• A significant mean reduction of 83.1% in NKA was observed on POD1 compared to baseline (p < 0.0001), meeting the primary endpoint.
• Profound NKA suppression persisted, with 65.5% and 33.3% of patients showing <75% baseline levels on POD28 and POD56, respectively.
• NKC was reduced by 24.6% on POD1 (p=0.0024), but immune cell profiling showed no significant changes in NK cell numbers or subsets.

Conclusions:

• NK cell IFNγ secretion (NKA) is significantly suppressed for up to two months after colorectal cancer surgery.
• This represents a more severe degree of surgery-induced immunosuppression than previously reported.
• The prolonged suppression of NKA warrants further investigation into its implications for postoperative outcomes, including cancer metastasis.