Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma
Abstract Background Activated regulatory T cells (aTregs) play a vital role in promoting a tumor immunosuppressive microenvironment in laryngeal squamous cell carcinoma (LSCC). However, the regulatory factors that induce the generation of aTregs are not clear. Herein, we investigated the effect of a...
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| Materiálatiipa: | Artihkal |
| Giella: | English |
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BMC
2024-10-01
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| Ráidu: | Head & Face Medicine |
| Fáttát: | |
| Liŋkkat: | https://doi.org/10.1186/s13005-024-00466-6 |
| _version_ | 1827014987943510016 |
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| author | Hang Li Ruihua Fang Renqiang Ma Yudong Long Rui He Huanhuan Lyu Lin Chen Yihui Wen |
| author_facet | Hang Li Ruihua Fang Renqiang Ma Yudong Long Rui He Huanhuan Lyu Lin Chen Yihui Wen |
| author_sort | Hang Li |
| collection | DOAJ |
| description | Abstract Background Activated regulatory T cells (aTregs) play a vital role in promoting a tumor immunosuppressive microenvironment in laryngeal squamous cell carcinoma (LSCC). However, the regulatory factors that induce the generation of aTregs are not clear. Herein, we investigated the effect of amphiregulin (AREG) on the production of aTregs in the tumor microenvironment of LSCC. Methods Immunohistochemical (IHC) analysis was conducted to examine the expression of AREG and FOXP3, and their association with clinical parameters and patient outcomes was demonstrated. The expression level of EGFRs in three functional subsets of Tregs was assessed, and the induction of CD4+ T cells into aTregs in the presence or absence of AREG or Gefitinib was analyzed using flow cytometry. Results Our results showed a higher expression level of AREG was significantly related to advanced clinical stage and worse survival, particularly with increased infiltration of Tregs in LSCC tumor tissue. The in vitro study showed that AREG significantly promoted the differentiation of aTregs, and enhanced the inhibitory effect of Tregs on T cell proliferation, which could be reversed by epidermal growth factor receptor (EGFR) inhibitors. In addition, we found that EGFR was highly expressed in aTregs, but not in other subsets of Tregs. It is suggested that AREG might induce aTregs, and enhance the immunosuppressive function of Tregs via the AREG/EGFR signal pathway. Conclusions Collectively, this study revealed the role and mechanism of AREG in negative immune regulation, and targeting AREG might be a novel immunotherapy for LSCC. |
| first_indexed | 2025-02-18T14:16:35Z |
| format | Article |
| id | doaj.art-f27f588e9d8b4f0aa02676a9ecc41b51 |
| institution | Directory Open Access Journal |
| issn | 1746-160X |
| language | English |
| last_indexed | 2025-02-18T14:16:35Z |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Head & Face Medicine |
| spelling | doaj.art-f27f588e9d8b4f0aa02676a9ecc41b512024-10-28T09:12:03ZengBMCHead & Face Medicine1746-160X2024-10-012011910.1186/s13005-024-00466-6Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinomaHang Li0Ruihua Fang1Renqiang Ma2Yudong Long3Rui He4Huanhuan Lyu5Lin Chen6Yihui Wen7Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background Activated regulatory T cells (aTregs) play a vital role in promoting a tumor immunosuppressive microenvironment in laryngeal squamous cell carcinoma (LSCC). However, the regulatory factors that induce the generation of aTregs are not clear. Herein, we investigated the effect of amphiregulin (AREG) on the production of aTregs in the tumor microenvironment of LSCC. Methods Immunohistochemical (IHC) analysis was conducted to examine the expression of AREG and FOXP3, and their association with clinical parameters and patient outcomes was demonstrated. The expression level of EGFRs in three functional subsets of Tregs was assessed, and the induction of CD4+ T cells into aTregs in the presence or absence of AREG or Gefitinib was analyzed using flow cytometry. Results Our results showed a higher expression level of AREG was significantly related to advanced clinical stage and worse survival, particularly with increased infiltration of Tregs in LSCC tumor tissue. The in vitro study showed that AREG significantly promoted the differentiation of aTregs, and enhanced the inhibitory effect of Tregs on T cell proliferation, which could be reversed by epidermal growth factor receptor (EGFR) inhibitors. In addition, we found that EGFR was highly expressed in aTregs, but not in other subsets of Tregs. It is suggested that AREG might induce aTregs, and enhance the immunosuppressive function of Tregs via the AREG/EGFR signal pathway. Conclusions Collectively, this study revealed the role and mechanism of AREG in negative immune regulation, and targeting AREG might be a novel immunotherapy for LSCC.https://doi.org/10.1186/s13005-024-00466-6AmphiregulinEpidermal growth factor receptorLaryngeal squamous cell carcinomaImmunosuppressive microenvironmentRegulatory T cells |
| spellingShingle | Hang Li Ruihua Fang Renqiang Ma Yudong Long Rui He Huanhuan Lyu Lin Chen Yihui Wen Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma Head & Face Medicine Amphiregulin Epidermal growth factor receptor Laryngeal squamous cell carcinoma Immunosuppressive microenvironment Regulatory T cells |
| title | Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma |
| title_full | Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma |
| title_fullStr | Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma |
| title_full_unstemmed | Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma |
| title_short | Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma |
| title_sort | amphiregulin promotes activated regulatory t cell suppressive function via the areg egfr pathway in laryngeal squamous cell carcinoma |
| topic | Amphiregulin Epidermal growth factor receptor Laryngeal squamous cell carcinoma Immunosuppressive microenvironment Regulatory T cells |
| url | https://doi.org/10.1186/s13005-024-00466-6 |
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