Significance of M2-polarized tumor-associated macrophage in pancreatic cancer.
BACKGROUND
The roles of infiltrating macrophages within the tumor microenvironment are complex because of their functional variety. The aim of this study is to examine the role and prognostic significance of tumor-associated macrophages (TAMs) that have an M2 polarized function in pancreatic cancer.


METHODS
Formalin-fixed, paraffin-embedded blocks were obtained from 76 patients with pancreatic head cancer. All patients underwent macroscopic curative resection. We assessed the number of infiltrating macrophages within the tumor invasive front by not only CD68 but also by CD163 and CD204, which are specific receptors on M2-polarized macrophages. Furthermore, to evaluate lymphangiogenesis, we measured the density of lymphatic vessels in the tumor invasive front by using D2-40.


RESULTS
High incidence of lymph node metastasis was shown in cases with a high number of CD163- or CD204-positive macrophages. Significantly increased lymphatic vessel density (LVD) was shown in cases with lymph node metastasis compared with cases without lymph node metastasis (P=0.0094). Significantly increased LVD (P=0.0175) and a poor prognosis (P=0.0171) were shown in cases with a high number of macrophages that express CD163 or CD204, however, there was no significant difference according to the number of CD68-positive macrophages.


CONCLUSIONS
M2-polarized TAMs in the invasive front of pancreatic cancer are associated with a poor prognosis due to accelerated lymphatic metastasis, and inhibition of the functional interaction between M2-polarized TAMs and tumor cells may improve the prognosis.
Kurahara
Hiroshi
H
Department of Surgical Oncology and Digestive Surgery, Graduate School of Medical Science, Kagoshima University, Sakuragaoka, Kagoshima, Japan. h-krhr@m3.kufm.kagoshima-u.ac.jp
Shinchi
Hiroyuki
H
Mataki
Yuko
Y
Maemura
Kousei
K
Noma
Hidetoshi
H
Kubo
Fumitake
F
Sakoda
Masahiko
M
Ueno
Shinichi
S
Natsugoe
Shoji
S
Takao
Sonshin
S
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012189:Retrospective Studies; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C495139:MSR1 protein, human; D011956:Receptors, Cell Surface; D051117:Scavenger Receptors, Class A