Sakamoto Shuichi, Kagawa Shunsuke, Kuwada Kazuya, Ito Atene, Kajioka Hiroki, Kakiuchi Yoshihiko, Watanabe Megumi, Kagawa Tetsuya, Yoshida Ryuichi, Kikuchi Satoru, Kuroda Shinji, Tazawa Hiroshi, Fujiwara Toshiyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan.
Oncoimmunology. 2019 Oct 22;8(12):e1671760. doi: 10.1080/2162402X.2019.1671760. eCollection 2019.
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.
实体瘤由癌细胞和基质细胞组成，它们共同构成肿瘤微环境（TME）。肿瘤相关巨噬细胞（TAM）通常在TME中大量存在，促进肿瘤进展。在胃癌（GC）腹膜播散的情况下，腹腔内TAM的作用仍不清楚。分析了GC患者腹腔冲洗液中的巨噬细胞，并研究了腹腔内TAM与GC细胞之间的联系，以阐明它们在腹膜播散中的相互作用。巨噬细胞在构成腹膜腔微环境的白细胞中占主导地位。IV期GC中CD163阳性TAM的比例显著高于I期。与TAM共培养增强了GC的迁移和侵袭。在巨噬细胞与GC的体外共培养培养基中，IL-6增加最为明显，在有腹膜播散的腹腔冲洗液中也观察到IL-6升高。临床病例中，腹腔内IL-6浓度升高与预后不良相关。总之，腹腔内TAM通过分泌IL-6参与促进GC的腹膜播散。TAM来源的IL-6可能是GC腹膜播散的潜在治疗靶点。
