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.
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.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Keijiro
K
Sugimura
Hiroshi
H
Miyata
Koji
K
Tanaka
Tsuyoshi
T
Takahashi
Yukinori
Y
Kurokawa
Makoto
M
Yamasaki
Kiyokazu
K
Nakajima
Shuji
S
Takiguchi
Masaki
M
Mori
Yuichiro
Y
Doki
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
chemotherapy; esophageal cancer; macrophage