Perioperative arginine prevents metastases by accelerating natural killer cell recovery after surgery
Leonard Angka1, Christiano Tanese de Souza2, Katherine E Baxter2
1Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Abstract:
Profound natural killer (NK) cell suppression after cancer surgery is a main driver of metastases and recurrence, for which there is no clinically approved intervention available. Surgical stress is known to cause systemic postoperative changes that negatively modulate NK cell function including the expansion of surgery-induced myeloid-derived suppressor cells (Sx-MDSCs) and a marked reduction in arginine bioavailability. In this study, we determine that Sx-MDSCs regulate systemic arginine levels in the postoperative period and that restoring arginine imbalance after surgery by dietary intake alone was sufficient to significantly reduce surgery-induced metastases in our preclinical murine models. Importantly, the effects of perioperative arginine were dependent upon NK cells. Although perioperative arginine did not prevent immediate NK cell immunoparalysis after surgery, it did accelerate their return to preoperative cytotoxicity, interferon gamma secretion, and activating receptor expression. Finally, in a cohort of patients with colorectal cancer, postoperative arginine levels were shown to correlate with their Sx-MDSC levels. Therefore, this study lends further support for the use of perioperative arginine supplementation by improving NK cell recovery after surgery.
Insights
Dietary arginine supplementation can reduce cancer recurrence after surgery by restoring natural killer (NK) cell function. This approach addresses surgery-induced immune suppression and improves NK cell recovery, offering a potential intervention for cancer patients.
Area of Science:
- Immunology
- Oncology
- Surgical Pathology
Background:
- Cancer surgery can lead to natural killer (NK) cell suppression, increasing metastasis and recurrence risk.
- Surgical stress induces myeloid-derived suppressor cells (Sx-MDSCs) and reduces arginine bioavailability, impairing NK cell function.
- Currently, no approved interventions exist to counteract post-surgical NK cell suppression.
Purpose of the Study:
- To investigate the role of surgery-induced myeloid-derived suppressor cells (Sx-MDSCs) in regulating postoperative arginine levels.
- To determine if restoring arginine levels through dietary intake can mitigate surgery-induced metastases.
- To evaluate the impact of perioperative arginine on NK cell recovery and function.
Main Methods:
- Preclinical murine models were used to assess the effects of arginine supplementation on surgery-induced metastases.
- NK cell cytotoxicity, interferon gamma secretion, and activating receptor expression were measured.
- Arginine and Sx-MDSC levels were analyzed in a cohort of colorectal cancer patients post-surgery.
Main Results:
- Dietary arginine supplementation significantly reduced surgery-induced metastases in preclinical models.
- Perioperative arginine accelerated NK cell recovery, enhancing cytotoxicity and interferon gamma secretion.
- Postoperative arginine levels correlated with Sx-MDSC levels in colorectal cancer patients.
Conclusions:
- Surgery-induced myeloid-derived suppressor cells (Sx-MDSCs) regulate systemic arginine levels post-surgery.
- Restoring arginine balance via dietary intake is a viable strategy to reduce cancer recurrence.
- Perioperative arginine supplementation shows promise for improving NK cell recovery and function after cancer surgery.
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