Frequency, Suppressive Capacity, Recruitment and Induction Mechanisms of Regulatory T Cells in Sinonasal Squamous Cell Carcinoma and Nasal Inverted Papilloma
Background Sinonasal squamous cell carcinoma (SSCC) and nasal inverted papilloma (NIP) represent the predominant type of malignant and benign tumors in sinonasal tract, respectively. CD4(+)CD25(+)Foxp3(+) natural regulatory T (Treg) cells might play critical role(s) in the suppression of anti-tumor immune response and thus shed light on tumor progression from benign to malignant. Objective This study aimed to evaluate the frequency and suppressive capacity of Treg cells in SSCC compared to NIP and further to explore the underlying mechanisms. Patients and Methods Frequencies of Treg, Th1 and Th2 cells were evaluated by flow cytometry in tissue homogenate and peripheral blood from 31 SSCC patients, 32 NIP patients and 35 normal controls. Treg cells were tested for regulatory function by co-culture with effector T cells. CCR4 and its ligands, CCL22 and CCL17, were analyzed by flow cytometry and Luminex, respectively. The chemoattractant properties of CCR4/CCL22 and CCR4/CCL17 for Treg cells were assessed using the Boyden chamber technique, to elucidate the potential mechanisms of Treg recruitment in tumor microenvironment. Treg cells induction via TGF-beta was assessed with transwells after local CD4(+)Foxp3(+) T cells were assessed by immunohistochemistry and TGF-beta concentration was measured by Luminex. Results Tumor-infiltrating Treg cells increased significantly from normal to NIP to SSCC (P <= 0.001 for normal vs. NIP and P = 0.004 for NIP vs. SSCC). Significantly elevated frequency and enhanced suppression capacity of circulating Treg cells in SSCC were detected compared to NIP and healthy controls, concomitant with Th1 decrease and Th2 increase. Apparently increased CCL22 attracted CCR4-expressing Treg cells to tumor microenvironment in SSCC, compared to NIP. SSCC produced significantly more TGF-beta than NIP and thus possessed greater potential for Treg cell induction. Conclusion Frequency and suppressive capacity of Treg cells enhanced with progression of malignancy from NIP to SSCC. Circulating Treg cells were recruited to tumor tissue via CCR4/CCL22 signalling, whereas tumor-synthesised TGF-beta contributed to induction of peripheral Treg cells.
基金：
Program for Changjiang Scholars and Innovative
Research Team (IRT13082), the National Science
Fund for the Major International Joint Research
Program (81420108009), Beijing Natural Science
Foundation (7131006), Ministry of Health Foundation
(201202005), the Capital Health Research and
Development of Special (2011-1017-06), the Special
Fund of Sanitation Elite Reconstruction of Beijing (2009-2-007) and Beijing Health Bureau Program for
high level talents (2009-2-007 and 2011-3-043).
第一作者机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Lou Hongfei,Fang Jugao,Li Pingdong,et al.Frequency, Suppressive Capacity, Recruitment and Induction Mechanisms of Regulatory T Cells in Sinonasal Squamous Cell Carcinoma and Nasal Inverted Papilloma[J].PLOS ONE.2015,10(5):doi:10.1371/journal.pone.0126463.
APA：
Lou, Hongfei,Fang, Jugao,Li, Pingdong,Zhou, Weiguo,Wang, Yang...&Zhang, Luo.(2015).Frequency, Suppressive Capacity, Recruitment and Induction Mechanisms of Regulatory T Cells in Sinonasal Squamous Cell Carcinoma and Nasal Inverted Papilloma.PLOS ONE,10,(5)
MLA：
Lou, Hongfei,et al."Frequency, Suppressive Capacity, Recruitment and Induction Mechanisms of Regulatory T Cells in Sinonasal Squamous Cell Carcinoma and Nasal Inverted Papilloma".PLOS ONE 10..5(2015)
