The Impact of Tumor-associated Macrophages on Chemoresistance <i>via</i> Angiogenesis in Colorectal Cancer
Masatsune Shibutani, Shigetomi Nakao, Kiyoshi Maeda, Hisashi Nagahara, Shinichiro Kashiwagi, Kosei Hirakawa, Masaichi Ohira
Abstract
BACKGROUND/AIM: The tumor microenvironment plays an important role in tumor progression. Tumor-associated macrophages (TAMs) have been reported to promote proliferation, invasion, metastasis, angiogenesis, and immunosuppression. Furthermore, angiogenesis has been reported to induce chemoresistance due to the inefficient distribution of drugs to cancer cells. However, the impact of TAMs on chemoresistance via angiogenesis in colorectal cancer (CRC) remains unclear. The aim of the study was to evaluate the impact of TAMs on the chemotherapeutic outcome in CRC. PATIENTS AND METHODS: We enrolled 54 patients who underwent chemotherapy for unresectable metastatic CRC after resection of the primary tumor. We evaluated the density of TAMs and the degree of angiogenesis by immunohistochemistry and then explored the correlation between the density of TAMs and chemotherapeutic outcome. Furthermore, we assessed any correlation between the density of TAMs and that of neovascularity. RESULTS: The high-TAMs group had a significantly worse progression-free survival (p=0.0006) and a poorer response rate (p=0.0274) than the low-TAMs group. In addition, a positive correlation was observed between the density of TAMs and the degree of neovascularity (r=0.665, p=0.0004). CONCLUSION: TAMs were shown to promote chemoresistance via angiogenesis in CRC.