Functionally distinct subsets of CD4+ regulatory T cells in patients with laryngeal squamous cell carcinoma are indicative of immune deregulation and disease progression

Sun,Wei; Li,Wei-Jin; Fu,Qing-Ling; Wu,Chang-You; Lin,Ji-Zhen; Zhu,Xiao-Lin; Hou,Wei-Jian; Wei,Yi; Wen,Yi-Hui; Wang,Yue-Jian; Wen,Wei-Ping

doi:10.3892/or.2014.3553

Functionally distinct subsets of CD4+ regulatory T cells in patients with laryngeal squamous cell carcinoma are indicative of immune deregulation and disease progression

Authors:
- Wei Sun
- Wei-Jin Li
- Qing-Ling Fu
- Chang-You Wu
- Ji-Zhen Lin
- Xiao-Lin Zhu
- Wei-Jian Hou
- Yi Wei
- Yi-Hui Wen
- Yue-Jian Wang
- Wei-Ping Wen
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Affiliations: Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China, Institute of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P.R. China, Department of Otorhinolaryngology Head and Neck Surgery, University of Minnesota, Minneapolis, MN, USA, Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Foshan, Foshan, Guangdong, P.R. China
Published online on: October 20, 2014 https://doi.org/10.3892/or.2014.3553
Pages: 354-362

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Abstract

CD4+ regulatory T cells (Tregs) mediate immune tolerance in laryngeal squamous cell carcinoma (LSCC). However, Tregs are functionally heterogeneous. Recently, we reported that three distinct Treg subsets (resting Tregs, activated Tregs and cytokine-secreting CD45RA-Foxp3lowCD4+ T cells) vary in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC); however, the potential implication of these Treg subsets in LSCC immunity is unclear. Here, we report that activated Tregs and cytokine‑secreting CD45RA-Foxp3lowCD4+ T cells were increased in LSCC patients compared with healthy donors (HD) (p<0.001, p<0.001), whereas resting Tregs were decreased (p<0.001). Activated Tregs inhibited the proliferation of CD4+CD25- T cells (p<0.001) and secreted lower levels of interleukin-2 (p<0.001), interferon-γ (p<0.001) and tumor necrosis factor-α (p<0.001) compared with the cytokine-secreting CD45RA-Foxp3lowCD4+ T cells. Importantly, activated Treg prevalence was correlated with tumor stage (p=0.001) and nodal status (p=0.007). The prevalence of naïve CD4+ (p<0.001), naïve CD8+ (p=0.002), and Th1 T-cell subsets (p<0.001, p<0.001) was decreased in the LSCC patients. In conclusion, our findings showed that activated Tregs with suppressive activity are a distinct subset of Tregs in LSCC, and correlate with disease progression. Several immune system abnormalities in LSCC patients are represented by expansion of functionally activated Tregs, both in the circulation and tumor microenvironment along with decreased frequencies of naïve T-cell populations and Th1-cell populations.

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