title: Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection.
abstract: BACKGROUND
  Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system.
  
  
  METHODS
  We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients.
  
  
  RESULTS
  CD68(+) TAMs display polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c(+) TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206(+) TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p < 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p < 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes.
  
  
  CONCLUSIONS
  Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Key Laboratory of Glycoconjugate Research, Ministry of Health, Shanghai, China. jjxufdu@fudan.edu.cn.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road, PO Box 103, Shanghai, 200032, China. jjxufdu@fudan.edu.cn.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China. qin.jing@zs-hospital.sh.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, 180 Feng Lin Road, Shanghai, 200032, China. sun.yihong@zs-hospital.sh.cn.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D016764:Cell Polarity; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Gastric cancer; Nomogram; Overall survival; Prognosis; Tumor-associated macrophages