Perioperative arginine prevents metastases by accelerating natural killer cell recovery after surgery.

Autor:	Angka L; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada., Tanese de Souza C; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Baxter KE; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Khan ST; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Market M; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada., Martel AB; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON K1H 8L1, Canada., Tai LH; Department of Immunology & Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada., Kennedy MA; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Bell JC; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada., Auer RC; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Centre for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON K1H 8L1, Canada. Electronic address: rauer@toh.ca.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2022 Oct 05; Vol. 30 (10), pp. 3270-3283. Date of Electronic Publication: 2022 May 26.
DOI:	10.1016/j.ymthe.2022.05.024
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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