High CCR6/CCR7 expression and Foxp3+ Treg cell number are positively related to the progression of laryngeal squamous cell carcinoma

Oncol Rep. 2013 Sep;30(3):1380-90. doi: 10.3892/or.2013.2603. Epub 2013 Jul 8.


Chemokine receptors CCR6 and CCR7 have been reported to play important roles in T cell migration and organ-specific metastasis of various tumors. In the present study, we evaluated the expression and clinical significance of CCR6, CCR7, their ligands and CD4+CD25+Foxp3+ regulatory T cells in laryngeal squamous cell carcinoma (LSCC) and metastatic lymph nodes (LNs). The expression of CCR6, CCR7 and their ligands mRNA (CCL20, CCL19/CCL21) as well as the CCR6 and CCR7 proteins were detected by real-time RT-PCR and immunohistochemistry (IHC), respectively. Flow cytometry was used to investigate the percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs). Furthermore, a number of cytokines, including interleukin (IL)-2, IL-4, IL-10, IL-12p70, interferon (IFN)-γ and transforming growth factor (TGF)-β1 were detected by ELISA. The results showed that CCR6 and CCR7 were expressed in tumors in situ, metastatic LNs and CD4+CD25+Foxp3+ Tregs. It was hypothesized that the expression profile of CCR6, CCR7 and the proliferation of CD4+CD25+Foxp3+ Tregs affected the process of LN metastasis in LSCC patients. Therefore, the increased percentage of the Foxp3+ Tregs and the upregulation of Foxp3 expression on CCR6+ Tregs in LSCC patients may have accounted for the downregulation of antitumor immunity in these patients, which could be valuable for assessment of prognosis in LSCC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Laryngeal Neoplasms / immunology*
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, CCR6 / metabolism*
  • Receptors, CCR7 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • CCR6 protein, human
  • CCR7 protein, human
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger
  • Receptors, CCR6
  • Receptors, CCR7