Sugimura Keijiro, Miyata Hiroshi, Tanaka Koji, Takahashi Tsuyoshi, Kurokawa Yukinori, Yamasaki Makoto, Nakajima Kiyokazu, Takiguchi Shuji, Mori Masaki, Doki Yuichiro
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
J Surg Oncol. 2015 May;111(6):752-9. doi: 10.1002/jso.23881. Epub 2015 Mar 8.
Tumor-associated macrophages (TAMs) are well known to have distinct roles in tumor progression and metastasis. However, the role of TAMs in chemoresistance has not been fully investigated. The aim of this study is to examine whether TAMs, especially M2 macrophages, are associated with the tumor response to chemotherapy with esophageal cancers.
Using 210 tissues from patients with esophageal cancer who underwent surgery, we calculated the number of intratumoral CD68(+) macrophages, CD163(+) macrophages, and CD8(+) lymphocytes using immunohistochemistry. CD68 and CD163 were used as markers for whole macrophages and M2 macrophages, respectively.
Infiltration of CD68(+) macrophages and CD163(+) macrophages was significantly associated with tumor depth, lymphatic invasion, and venous invasion. High infiltration of CD68(+) macrophages and CD163(+) macrophages was significantly associated with poor prognosis for patients undergoing neoadjuvant chemotherapy. Regarding the response to chemotherapy, high infiltration of CD68(+) and CD163(+) macrophages had a significant association with poor response to chemotherapy, both clinically and pathologically (P < 0.001, P < 0.001). Multivariate analysis showed that infiltration of CD163(+) macrophages was an independent prognostic factor in patients undergoing neoadjuvant chemotherapy.
Infiltration of TAMs, especially M2 macrophages, is associated with a poor response to chemotherapy and poor prognosis of patients with esophageal cancer.
肿瘤相关巨噬细胞（TAM）在肿瘤进展和转移中具有不同作用，这已广为人知。然而，TAM在化疗耐药中的作用尚未得到充分研究。本研究旨在探讨TAM，尤其是M2巨噬细胞，是否与食管癌化疗反应相关。
我们使用210例接受手术治疗的食管癌患者的组织，通过免疫组织化学计算瘤内CD68（+）巨噬细胞、CD163（+）巨噬细胞和CD8（+）淋巴细胞的数量。CD68和CD163分别用作全巨噬细胞和M2巨噬细胞的标志物。
CD68（+）巨噬细胞和CD163（+）巨噬细胞浸润与肿瘤深度、淋巴浸润及静脉浸润显著相关。CD68（+）巨噬细胞和CD163（+）巨噬细胞的高浸润与接受新辅助化疗患者的不良预后显著相关。关于化疗反应，CD68（+）和CD163（+）巨噬细胞的高浸润在临床和病理上均与化疗反应不良显著相关（P<0.001，P<0.001）。多因素分析显示，CD163（+）巨噬细胞浸润是接受新辅助化疗患者的独立预后因素。
TAM，尤其是M2巨噬细胞的浸润与食管癌患者化疗反应不良及预后不良相关。
