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

• Published in: Oncology reports Vol. 30; no. 3; pp. 1380 - 1390
• Main Authors: CHEN, BIN, ZHANG, DUO, ZHOU, JIAN, LI, QING, ZHOU, LIN, LI, SHI-MIN, ZHU, LI, CHOU, KUANG-YEN, ZHOU, LIANG, TAO, LEI, LU, LI-MING
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.09.2013; Spandidos Publications UK Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Cancer therapies; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CCR6; CCR7; Chemokines; Chemotherapy; Cytokines; Cytokines - genetics; Cytokines - metabolism; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Follow-Up Studies; forkhead box P3; Forkhead Transcription Factors - metabolism; Growth factors; Humans; Immunoenzyme Techniques; Laryngeal cancer; Laryngeal Neoplasms - immunology; Laryngeal Neoplasms - metabolism; Laryngeal Neoplasms - pathology; laryngeal squamous cell carcinoma; Ligands; Lymphatic Metastasis; Lymphocytes; Male; Medical prognosis; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Pathogenesis; Patients; Prognosis; Real-Time Polymerase Chain Reaction; Receptors, CCR6 - metabolism; Receptors, CCR7 - metabolism; regulatory T cell; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Squamous cell carcinoma; Survival Rate; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2013.2603

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.