title: Intratumoral IL-17⁺ cells and neutrophils show strong prognostic significance in intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Inflammatory reactions at a tumor site have both detrimental and beneficial effects on tumor progression. This study was designed to assess the clinical significance of tumor-infiltrating inflammatory cells in patients with intrahepatic cholangiocarcinoma (ICC).
  
  
  METHODS
  A total of 123 consecutive ICC patients who underwent curative resection were enrolled. Tissue microarray and immunohistochemistry were used to analyze the distribution and clinical relevance of IL-17(+), FOXP3(+), CD8(+), CD66b(+) cells, and microvessel density (CD34) in different microanatomical areas.
  
  
  RESULTS
  IL-17(+) cells, FOXP3(+) lymphocytes, CD66b(+) neutrophils, and microvessels were enriched predominantly in intratumor (IT) area, whereas CD8(+) lymphocytes were most abundant in tumor invasive front. On univariate analyses, increasing IL-17 (IT) (+) and neutrophils(IT) were significantly associated with worse patient survival. Multivariate analyses revealed that IL-17 (IT) (+) (hazard ratio [HR] = 1.59; 95% confidence interval [CI], 1.05-2.41; P = 0.028), neutrophils(IT) (HR = 1.76; 95% CI, 1.16-2.65; P = 0.007), and their combination (HR 2.8; 95% CI 1.72-4.57; P < 0.001) were independent prognostic factors, which were superior to conventional clinicopathologic features, such as intrahepatic metastasis and TNM stage. IL-17 (IT) (+) significantly correlated with the presence of lymph node metastasis, intrahepatic metastasis, and advanced stages, whereas neutrophils(IT) correlated with the presence of vascular invasion. In addition, significant positive correlations were detected among densities of IL-17(+) cells, neutrophils, and microvessel density.
  
  
  CONCLUSIONS
  Our data suggested that intratumor IL-17(+) cells, neutrophils are novel, powerful predictors of prognosis in patients with ICC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai, People's Republic of China.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Gu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiping
authors.initials: J
authors.lastname: Wang
authors.forename: Jia-Hao
authors.initials: JH
authors.lastname: Jiang
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Zhen-Bin
authors.initials: ZB
authors.lastname: Ding
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000401:mortality* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D058504:Th17 Cells / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult