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Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer
OncoImmunology ( IF 6.5 ) Pub Date : 2019-10-22 , DOI: 10.1080/2162402x.2019.1671760
Shuichi Sakamoto 1 , Shunsuke Kagawa 1, 2 , Kazuya Kuwada 1 , Atene Ito 1 , Hiroki Kajioka 1 , Yoshihiko Kakiuchi 1 , Megumi Watanabe 1 , Tetsuya Kagawa 1 , Ryuichi Yoshida 1 , Satoru Kikuchi 1, 2 , Shinji Kuroda 1, 3 , Hiroshi Tazawa 1, 3 , Toshiyoshi Fujiwara 1
Affiliation  

A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC.

中文翻译:

腹膜癌免疫微环境促进胃癌的腹膜扩散

实体瘤由癌症和基质细胞组成,它们包括肿瘤微环境(TME)。肿瘤相关巨噬细胞(TAM)通常在TME中丰富,有助于肿瘤进展。在腹膜扩散性胃癌(GC)的情况下,腹膜内TAM的作用仍不清楚。分析了胃癌患者腹膜冲洗液中的巨噬细胞,并研究了腹膜内TAMs和GC细胞之间的联系,以阐明它们在腹膜扩散中的相互作用。在构成腹膜腔微环境的白细胞中,巨噬细胞占主导地位。IV期CD163阳性TAM的比例显着高于I GC期。与TAM的共培养可增强GC的迁移和侵袭。IL-6在巨噬细胞和GC的体外共培养培养基中增加最多,在腹膜清洗和腹膜扩散中也观察到IL-6升高。腹膜内IL-6浓度升高与临床病例预后不良有关。总之,腹膜内TAM参与通过分泌的IL-6促进腹膜GC的扩散。TAM衍生的IL-6可能是GC腹膜传播的潜在治疗靶标。
更新日期:2019-10-25
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