Preventing postoperative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells

Area of Science:

• Immunology
• Oncology
• Surgical Science

Background:

• Postoperative metastases are a significant concern in cancer surgery.
• Natural killer (NK) cells are crucial for clearing tumor cells and preventing metastasis.
• Surgical stress is suspected to impair NK cell function, but direct evidence is limited.

Purpose of the Study:

• To investigate the impact of surgical stress on NK cell function and its role in postoperative metastasis.
• To evaluate the efficacy of perioperative oncolytic viral therapy in restoring NK cell function and reducing metastasis.

Main Methods:

• A mouse model of surgical stress was used to assess NK cell function and metastasis.
• NK cells from surgically stressed mice were transferred to NK-deficient mice.
• Tumor cell killing assays (ex vivo and in vivo) were performed.
• Perioperative administration of oncolytic viruses (ORFV, vaccinia virus) was evaluated.
• Human studies assessed NK cell cytotoxicity in postoperative cancer patients.

Main Results:

• Surgical stress significantly reduced NK cell numbers, migration, and tumor cell killing capacity.
• Surgically stressed mice exhibited enhanced lung metastases compared to controls.
• Perioperative oncolytic virus administration reversed NK cell suppression and reduced metastasis.
• Postoperative cancer patients showed reduced NK cell cytotoxicity.
• Oncolytic vaccinia virus increased NK cell activity in cancer patients.

Conclusions:

• Surgical stress impairs global NK cell function, contributing to postoperative cancer metastasis.
• Perioperative oncolytic viral therapy represents a promising strategy to enhance NK cell activity.
• Targeting NK cell function perioperatively may reduce metastatic recurrence and improve survival in cancer patients.