Regulatory T cells, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma

BJU Int. 2013 Sep;112(5):686-96. doi: 10.1111/bju.12068. Epub 2013 Mar 15.


Objective: To identify a phenotype that could be informative and prognostic in patients with renal cell carcinoma (RCC) peripheral blood was evaluated for TH1, TH2, regulatory T cells (Tregs), natural killer (NK) and NKT cells and for cytokines/chemokines.

Patients and methods: Peripheral blood from 77 patients with RCC and 40 healthy controls was evaluated by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RA, CD45RO, CD152, CD184, CD279, CD3, CD16, CD56, CD161, CD158a, CD4, CD26, CD30, CD183 and CD184. A concomitant evaluation of 38 molecules was conducted in patients' serum using a multiplex biometric ELISA-based immunoassay.

Results: The number of NK cells CD3⁻/CD16⁺, CD3⁻/CD16⁺/CD161⁺ (NK) and CD3⁻/CD16⁺/CD161⁺/CD158a⁺ (NK- Kir 2+) was greater in the patients with RCC (P < 0.05); and the number of Treg cells CD4⁺/CD25(high+)/FOXP3⁺ and the subset CD4⁺/CD25(high+)/FOXP3⁺/CD45RA⁺ (naïve) and CD45R0⁺(memory) cells, were greater in the patients with RCC (P < 0.001). An increase in the following was observed in the serum of patients with RCC compared with healthy controls: interleukin (IL)-4, IL-6, IL-8, IL-10, G-CSF, CXCL10, CXCL11, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). According to Ingenuity Pathway Analysis (IPA), CXCL10, IL-6, IL-8, epidermal growth factor (EGF), HGF and VEGF were associated with a network that controls cellular movement, tissue development and cellular growth. Kaplan-Meier analysis for disease-free survival showed that high numbers of CD4⁺/CD25(high+)/FOXP3⁺/CD45RA⁺ (Treg naïve) and low numbers of CD3⁻/CD16⁺/CD161⁺/CD158a⁺ (NK-Kir+) cells predict short disease-free survival in patients with RCC.

Conclusion: Concomitant evaluation of Treg (CD4⁺/CD25(high+)/FOXP3⁺ and CD4⁺/CD25(high+)/FOXP3⁺/CD45RA⁺) and of six soluble factors (IL-6, IL-8 ,VEGF, CXCL10, CXCL11, EGF, HGF) might be a surrogate marker of host immunity in patients with RCC.

Keywords: NK; Treg; chemokine; cytokine; growth factors; renal cell carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL11 / metabolism
  • Disease Progression
  • Disease-Free Survival
  • Epidermal Growth Factor / metabolism
  • Female
  • Flow Cytometry
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Immunophenotyping
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Killer Cells, Natural / immunology*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory* / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Biomarkers
  • CXCL10 protein, human
  • CXCL11 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Interleukin-6
  • Interleukin-8
  • Vascular Endothelial Growth Factor A
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor