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.

癌症手术后严重的自然杀伤 (NK) 细胞抑制是转移和复发的主要驱动因素，目前尚无临床批准的干预措施。众所周知，手术应激会导致全身性术后变化，对 NK 细胞功能产生负调节，包括手术诱导的骨髓源性抑制细胞 (Sx-MDSC) 的扩张和精氨酸生物利用度的显着降低。在这项研究中，我们确定 Sx-MDSC 在术后期间调节全身精氨酸水平，并且在我们的临床前小鼠模型中，仅通过饮食摄入来恢复术后精氨酸失衡足以显着减少手术引起的转移。重要的是，围手术期精氨酸的作用取决于 NK 细胞。尽管围手术期精氨酸不能阻止术后 NK 细胞立即免疫麻痹，但它确实加速了它们恢复到术前的细胞毒性、干扰素 γ 分泌和激活受体表达。最后，在一组结直肠癌患者中，术后精氨酸水平与他们的 Sx-MDSC 水平相关。因此，这项研究通过改善术后 NK 细胞的恢复，为围手术期补充精氨酸提供了进一步的支持。