title: High CCR6/CCR7 expression and Foxp3+ Treg cell number are positively related to the progression of laryngeal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Kuang-Yen
authors.initials: KY
authors.lastname: Chou
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054399:Receptors, CCR6 / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; C515370:CCR7 protein, human; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D054399:Receptors, CCR6; D054400:Receptors, CCR7