Abstract 5011: Tumor associated macrophages promote malignant phenotypes of disseminated human gastric cancer cells in intraperitoneal cancer immune microenvironment

Abstract

Abstract Gastric cancer is the third leading cause of cancer-related death, and peritoneal dissemination is one of the most frequent site of recurrence. Although the role of tumor microenvironment is recognized, it is still unclear how intraperitoneal cancer-immune microenvironment contributes to peritoneal metastasis. Thus, we investigated the interaction between intraperitoneal cancer and immune cells, especially focusing on tumor-associated macrophages (TAM) in the peritoneal cavity. The peritoneal wash from gastric cancer patients was subjected to conventional cytology, flow cytometry, and immuno-fluorescent assay using antibodies against CD45 (leukocytes), CD14 (monocytes), CD80/163 (M1/M2 macrophages, respectively), in combination with genetically engineered cancer-imaging viral agent ‘TelomeScan’ which specifically expresses GFP in telomerase-positive cells. In cytology-positive samples, CD163-positive macrophages could be detected in approximately 70% of intraperitoneal macrophages with TelomeScan-positive cancer cells, while cytology negative samples contained few CD163-positive macrophages. In addition, peripheral blood mononuclear cells (PBMCs) from healthy volunteers were induced to differentiate into CD163-positive M2 macrophages (TAM-like macrophages), and co-cultured with gastric cancer cells to examine the effect on their malignant phenotype such as migration and invasion. We found that PBMCs-derived CD163-positive M2 macrophages significantly potentiated the ability of migration and invasion in gastric cancer cells. In case of existence of free cancer cells in peritoneal cavity, intraperitoneal macrophages appeared to differentiate into TAM and they potentially accelerate malignant phenotypes of gastric cancer cells. These results suggested that intraperitoneal cancer-immune microenvironment may play an important role to promote peritoneal disseminations in gastric cancer. Citation Format: Shuichi Sakamoto, Shunsuke Kagawa, Kazuya Kuwada, Atene Ito, Tetsuya Kagawa, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Hiroshi Tazawa, Toshiyoshi Fujiwara. Tumor associated macrophages promote malignant phenotypes of disseminated human gastric cancer cells in intraperitoneal cancer immune microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5011. doi:10.1158/1538-7445.AM2017-5011