Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1+ cells in intraperitoneal lavage fluid during gastric cancer surgery. Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1+ cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array. CX3CR1high patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1low patients. CX3CR1high patients tended to exhibit higher pathological T and N stage than CX3CR1low patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death–1 expression. Our results suggest that CX3CR1+ cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1+ cells could be useful for characterizing the immune environment after gastric cancer surgery.

中文翻译：

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胃癌术后立即出现在免疫抑制环境中腹腔中出现的CX3CR1+细胞的参与

胃癌主要通过手术治疗；然而，人们对腹膜内免疫环境的变化和手术对预后的影响知之甚少。手术压力和癌症相关炎症导致免疫细胞通过多种细胞因子动员到腹腔。其中一种细胞因子 CX3CR1 具有多种免疫相关功能，这些功能仍有待充分解释。我们通过研究胃癌手术期间腹腔灌洗液中的 CX3CR1+ 细胞来表征腹腔内免疫环境。灌洗液样本取自 41 名接受胃切除术的患者。使用定量实时PCR分析各种基因的相对表达。检查了每个基因表达与临床病理特征和手术结果的关联。通过流式细胞术分析CX3CR1+细胞的分数。使用细胞计数珠阵列研究灌洗液样品中的细胞因子谱。与 CX3CR1low 患者相比，CX3CR1high 患者在血液检查中表现出更高水平的围手术期炎症，且复发率更高。CX3CR1high 患者往往比 CX3CR1low 患者表现出更高的病理 T 和 N 分期。CX3CR1 主要在骨髓源性抑制细胞和肿瘤相关巨噬细胞上表达。特别是，多形核骨髓源性抑制细胞与围手术期炎症、病理性 N 和复发相关。这些免疫抑制细胞与不良预后的趋势相关。此外，CX3CR1 表达与程序性死亡-1 表达相关。我们的结果表明 CX3CR1+ 细胞与急性炎症反应、肿瘤促进和复发相关。CX3CR1 表达可以作为未来改善免疫抑制状态的有益治疗靶点。此外，腹内 CX3CR1+ 细胞的分析可用于表征胃癌手术后的免疫环境。