PMID- 25333227 OWN - NLM STAT- MEDLINE DCOM- 20150928 LR - 20171116 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 33 IP - 1 DP - 2015 Jan TI - Functionally distinct subsets of CD4(+) regulatory T cells in patients with laryngeal squamous cell carcinoma are indicative of immune deregulation and disease progression. PG - 354-62 LID - 10.3892/or.2014.3553 [doi] AB - 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-gamma (p<0.001) and tumor necrosis factor-alpha (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 naive CD4+ (p<0.001), naive 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 naive T-cell populations and Th1-cell populations. FAU - Sun, Wei AU - Sun W AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Li, Wei-Jin AU - Li WJ AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Fu, Qing-Ling AU - Fu QL AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Wu, Chang-You AU - Wu CY AD - Institute of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Lin, Ji-Zhen AU - Lin JZ AD - Department of Otorhinolaryngology Head and Neck Surgery, University of Minnesota, Minneapolis, MN, USA. FAU - Zhu, Xiao-Lin AU - Zhu XL AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Hou, Wei-Jian AU - Hou WJ AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Wei, Yi AU - Wei Y AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Wen, Yi-Hui AU - Wen YH AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. FAU - Wang, Yue-Jian AU - Wang YJ AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Foshan, Foshan, Guangdong, P.R. China. FAU - Wen, Wei-Ping AU - Wen WP AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141020 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (IL2RA protein, human) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Case-Control Studies MH - Disease Progression MH - Female MH - Forkhead Transcription Factors/metabolism MH - Humans MH - Interleukin-2 Receptor alpha Subunit/metabolism MH - Laryngeal Neoplasms/*immunology/pathology MH - Leukocyte Common Antigens/metabolism MH - Lymphocyte Subsets/immunology MH - Male MH - Middle Aged MH - Neoplasms, Squamous Cell/*immunology/pathology MH - Reference Values MH - T-Lymphocytes, Regulatory/*immunology/metabolism MH - Th1 Cells/immunology EDAT- 2014/10/22 06:00 MHDA- 2015/09/29 06:00 CRDT- 2014/10/22 06:00 PHST- 2014/06/26 00:00 [received] PHST- 2014/10/07 00:00 [accepted] PHST- 2014/10/22 06:00 [entrez] PHST- 2014/10/22 06:00 [pubmed] PHST- 2015/09/29 06:00 [medline] AID - 10.3892/or.2014.3553 [doi] PST - ppublish SO - Oncol Rep. 2015 Jan;33(1):354-62. doi: 10.3892/or.2014.3553. Epub 2014 Oct 20.