Abstract 635: Effects of vagus nerve signals on the development of peritoneal metastasis of murine gastric cancer
Authors: Futoh Yurie , Miyato Hideyo , Matsumiya Misaki , Takahashi Rei , Kaneko Yuki , Takahashi Kazuya , Kimura Yuki , Hayakawa Hiroko , Ohzawa Hideyuki , Sata Naohiro , Kitayama Joji 
Published: June 2023

Background: Vagus nerve is the only pathway that transmits parasympathetic signals between the brain and intraabdominal organs. Vagus nerve is often resected in the process of lymph node dissection in surgery for upper gastrointestinal tract malignancies. Several studies have shown that vagus nerve controls immune cell functions in abdominal organs through so called “cholinergic anti-inflammatory pathway’, which may seriously affect the tumor progression. However, the effect of vagotomy on postoperative outcome of the patients with gastric cancer is unclear.

Methods: We investigated the effects of vagotomy on the intraperitoneal immunity and the development of peritoneal dissemination of gastric cancer in murine model. C57BL/6 mice were divided into two groups and subjected to sub-diaphragmatic vagotomy with pyloroplasty (VxPP) or sham operation with vagus-nerve preservation (PP). Then, YTN16P, syngenic murine gastric cancer cell line, were injected in the peritoneal cavity of these mice and number of peritoneal metastases on the mesentery and omentum was counted after 2 weeks. Immune cells were collected from peritoneal lavage or spleen and the ratio or numbers of lymphocytes and granulocyte subsets, including large peritoneal macrophage (LPM), small peritoneal macrophage (SPM), neutrophil, eosinophil, were analyzed at several points using flow cytometry.

Results: The ratios of LPM, SPM and neutrophil almost unchanged at the 2weeks after surgery. However, the expression level of F4/80 of LPM in VxPP group decreased as compared with that in PP group (Mean Fluorescent Intensity; PP: 4510 ± 3610 vs VxPP: 660 ± 300, n=3). The ratio of regulatory T cell (Treg) in the spleen decreased at 2 weeks, but recovered to the preoperative levels 3 weeks after operation. There was no significant difference in the number of metastatic nodules on the mesentery between two groups (PP: 52.9 ± 24.6 vs VxPP: 62.8 ± 18.1, p=0.25, n=13). However, the number of nodules on the omentum in VxPP group was significantly greater than that in PP group (PP:2.8 ± 1.8 vs VxPP:5.2 ± 2.4, p&lt;0.01, n=13). The ratios of neutrophil in peritoneal lavage (PP: 17.6 ± 8.4% vs VxPP: 24.4 ± 7.6%, p=0.027, n=13) and G-MDSC/M-MDSC (PP: 1.8 ± 0.33% vs VxPP 2.77 ± 0.84%, p=0.0012, n=13) were greater, while that of LPM was less (PP:19.7 ± 17.4% vs VxPP 7.4 ± 4.1%, p&lt;0.01, n=13) in VxPP group, those in PP group.

Conclusion: Vagus nerve signal might control the frequency of macrophages and granulocytes in the peritoneal cavity, which may elicit inhibitory effect on the development of dissemination of gastric cancer to omentum.

Citation Format: Yurie Futoh, Hideyo Miyato, Misaki Matsumiya, Rei Takahashi, Yuki Kaneko, Kazuya Takahashi, Yuki Kimura, Hiroko Hayakawa, Hideyuki Ohzawa, Naohiro Sata, Joji Kitayama. Effects of vagus nerve signals on the development of peritoneal metastasis of murine gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 635.