title: Prognostic value of diametrically polarized tumor-associated macrophages in renal cell carcinoma.
abstract: BACKGROUND
  As the most abundant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are significant for fostering tumor progression. CD68(+) TAMs display diversely polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2). The aim of this study was to determine the survival impact of diametrically polarized TAMs in clear-cell renal cell carcinoma (ccRCC) and their application to stratification of patients according to their prognostic values.
  
  
  METHODS
  The study included 185 consecutive patients with ccRCC who underwent nephrectomy between 1999 and 2001. CD68(+) total and diametrically polarized (CD11c(+) M1 and CD206(+) M2) TAM densities were assessed by immunohistochemistry, and the relationships with clinicopathologic features and prognosis were evaluated.
  
  
  RESULTS
  Low CD11c(+) TAM density and high CD206(+) TAM density were associated with reduced cancer-specific survival (P = 0.043 and P = 0.017, respectively), whereas CD68(+) TAM density only had borderline prognostic significance (P = 0.062). Furthermore, combined analysis of CD11c(+) and CD206(+) TAMs (CD11c/CD206 signature) had a better power to predict patients' outcome (P = 0.010). Together with TNM stage, tumor necrosis, and performance status, CD11c/CD206 signature was an independent prognostic factor (P = 0.010). When applied to the University of California Integrated Staging System intermediate-/high-risk group for localized ccRCC, CD11c/CD206 signature could further distinguish patients with dismal prognosis (P = 0.004).
  
  
  CONCLUSIONS
  Intratumoral balance of diametrically polarized TAMs is a novel independent predictor for survival in patients with ccRCC. Tipping the balance toward an antitumoral phenotype might be a promising target of postoperative adjuvant therapy.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lian
authors.initials: L
authors.lastname: Chen
authors.forename: Huimin
authors.initials: H
authors.lastname: An
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Guomin
authors.initials: G
authors.lastname: Wang
authors.forename: Zongming
authors.initials: Z
authors.lastname: Lin
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor