title: Tumor-infiltrating regulatory T cells are positively correlated with angiogenic status in renal cell carcinoma.
abstract: BACKGROUND
  Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC.
  
  
  METHODS
  Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations.
  
  
  RESULTS
  Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05).
  
  
  CONCLUSIONS
  These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.
authors.affiliation: Department of Urology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ning
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Shao
authors.forename: Ke-Jia
authors.initials: KJ
authors.lastname: Ding
authors.forename: De-Xuan
authors.initials: DX
authors.lastname: Gao
authors.forename: Qing-le
authors.initials: QL
authors.lastname: Lu
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Cao
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Niu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Chun-Huan
authors.initials: CH
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.forename: Jia-Ju
authors.initials: JJ
authors.lastname: Lü
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*