Open AccessRole of tumor‐associated macrophages at the invasive front in human colorectal cancer progression
Author(s) -
Inagaki Katsuaki,
Kunisho Shoma,
Takigawa Hidehiko,
Yuge Ryo,
Oka Shiro,
Tanaka Shinji,
Shimamoto Fumio,
Chayama Kazuaki,
Kitadai Yasuhiko
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14940
Subject(s) - colorectal cancer , medicine , lymphovascular invasion , metastasis , cd163 , lymph node , tumor progression , cancer , pathology , oncology , cancer research , macrophage , biology , in vitro , biochemistry
Macrophages are an essential component of antitumor activity; however, the role of tumor‐associated macrophages (TAMs) in colorectal cancer (CRC) remains controversial. Here, we elucidated the role of TAMs in CRC progression, especially at the early stage. We assessed the TAM number, phenotype, and distribution in 53 patients with colorectal neoplasia, including intramucosal neoplasia, submucosal invasive colorectal cancer (SM‐CRC), and advanced cancer, using double immunofluorescence for CD68 and CD163. Next, we focused on the invasive front in SM‐CRC and association between TAMs and clinicopathological features including lymph node metastasis, which were evaluated in 87 SM‐CRC clinical specimens. The number of M2 macrophages increased with tumor progression and dynamic changes were observed with respect to the number and phenotype of TAMs at the invasive front, especially at the stage of submucosal invasion. A high M2 macrophage count at the invasive front was correlated with lymphovascular invasion, low histological differentiation, and lymph node metastasis; a low M1 macrophage count at the invasive front was correlated with lymph node metastasis. Furthermore, receiver operating characteristic curve analysis revealed that the M2/M1 ratio was a better predictor of the risk of lymph node metastasis than the pan‐, M1, or M2 macrophage counts at the invasive front. These results suggested that TAMs at the invasive front might play a role in CRC progression, especially at the early stages. Therefore, evaluating the TAM phenotype, number, and distribution may be a potential predictor of metastasis, including lymph node metastasis, and TAMs may be a potential CRC therapeutic target.