title: M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma.
abstract: OBJECTIVE
  Tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. However, the activated phenotype (M1 or M2) of tumor-associated macrophages remains unknown in solid tumors. Therefore, this study examined the density and prognostic significance of M2-polarized tumor-associated macrophages in lung adenocarcinoma.
  
  
  METHODS
  Tumor specimens from 65 lung adenocarcinoma patients were assessed by ELISA for Th1/Th2 cytokine concentrations. The activated phenotype (M1 or M2) of tumor-associated macrophages was determined utilizing immunofluorescence staining. Additionally, to evaluate lymphangiogenesis, peritumoral lymphatic microvessel density was measured using D2-40. The correlation between tumor-associated macrophage subtype and overall patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test.
  
  
  RESULTS
  A shift toward Th2 cytokine expression was detected within lung adenocarcinoma microenvironments. Approximately 79.71±16.27% of tumor-associated macrophages were M2 polarized; the remaining 20.35±5.31% were M1 polarized. The infiltration of M2-polarized macrophages was significantly associated with P-TNM staging and lymph node metastasis. The peritumoral lymphatic microvessel density was significantly higher in the high M2-polarized tumor-associated macrophage group than in the low M2-polarized tumor-associated macrophage group. A significant difference in overall patient survival was detected not only between patients with tumors with high and low macrophage counts but also between patients with tumors with high and low counts of M2-polarized macrophages.
  
  
  CONCLUSIONS
  Tumor-associated macrophages in lung adenocarcinoma have an M2-polarized subtype and are associated with poor prognoses, perhaps resulting from accelerated lymphangiogenesis and lymph node metastasis.
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People’s Liberation Army, Wuhan, Hubei Province, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Zhang
authors.forename: Guoqing
authors.initials: G
authors.lastname: Yao
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Rao
authors.forename: Jianfei
authors.initials: J
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000473:pathology*; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011379:Prognosis
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