Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery

Surgical resection is the foundation for the curative treatment of solid tumors. However, metastatic recurrence due to the difficulty in eradicating micrometastases remain a feared outcome. Paradoxically, despite the beneficial effects of surgical removal of the primary tumor, the physiological stress resulting from surgical trauma serves to promote cancer recurrence and metastasis. The postoperative environment suppresses critical anti-tumor immune effector cells, including Natural Killer (NK) cells. The literature suggests that NK cells are critical mediators in the formation of metastases immediately following surgery. The following review will highlight the mechanisms that promote the formation of micrometastases by directly or indirectly inducing NK cell suppression following surgery. These include tissue hypoxia, neuroendocrine activation, hypercoagulation, the pro-inflammatory phase, and the anti-inflammatory phase. Perioperative therapeutic strategies designed to prevent or reverse NK cell dysfunction will also be examined for their potential to improve cancer outcomes by preventing surgery-induced metastases.