High infiltration of tumor‐associated macrophages is associated with a poor response to chemotherapy and poor prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer

Abstract

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Infiltration of TAMs, especially M2 macrophages, is associated with a poor response to chemotherapy and poor prognosis of patients with esophageal cancer.