Editors' ChoiceCancer Immunology

Reactivating the Natural Killer

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Science Translational Medicine  14 Nov 2012:
Vol. 4, Issue 160, pp. 160ec207
DOI: 10.1126/scitranslmed.3005303

Human immune cells scan the body for various microbes, pathogens, and even tumor cells to attack. There are several possible ways that tumor cells can escape this immune surveillance. Surgery, for example, has been shown to affect immune cell function in the postoperative period by altering the function of natural killer (NK) cells, which are cytotoxic lymphocytes that play a major role in host clearance of malignant cells. Tai and colleagues explore this link between surgery and dysfunctional immune surveillance.

Tai et al. isolated NK cells from the spleen of rodents and the blood from patients undergoing tumor resection and demonstrated that NK cell function was significantly diminished after surgery. The human NK cells had reduced ability to kill tumor cells for up to 28 days after surgery. In rodent models, they found that the diminished NK cell function after surgery was linked to increased numbers of lung metastases. The authors linked the NK cell dysfunction after surgery to a number of factors, including NK cell sequestration into the surgical site, down-regulation of proteins responsible for NK cell activation, and alterations in the systemic levels of cytokines that modulate NK cell activity, such as interleukin-5 (IL-5), IL-6, and granulocyte colony-stimulating factor. In order to prevent NK cell dysfunction, Tai et al. treated animals with immune-stimulating oncolytic viruses immediately before surgery. They found that the viruses maintained NK cell activity and reduced the levels of distant tumor spread after surgery in rodents. Although the exact mechanism is unclear, the authors demonstrated that levels of interferon-γ, a known stimulant of NK cell activity, was up-regulated after virus administration.

This study suggests that surgical stress–induced blunting of NK cell function is reversible through treatment with immune-modulating agents. However, clinical trials will be required to demonstrate that maintenance of NK cell activity in human cancer patients can reduce tumor progression.

L Tai et al., Preventing post-operative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells. Cancer Research, published online 22 October 2012 (10.1158/0008-5472.CAN-12-1993). [Full Text]

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