Amphiregulin promotes activated regulatory T cell-suppressive function via the AREG/EGFR pathway in laryngeal squamous cell carcinoma.
Amphiregulin
Epidermal growth factor receptor
Immunosuppressive microenvironment
Laryngeal squamous cell carcinoma
Regulatory T cells
Journal
Head & face medicine
ISSN: 1746-160X
Titre abrégé: Head Face Med
Pays: England
ID NLM: 101245792
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
25
06
2024
accepted:
17
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
26
10
2024
Statut:
epublish
Résumé
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. 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 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. Collectively, this study revealed the role and mechanism of AREG in negative immune regulation, and targeting AREG might be a novel immunotherapy for LSCC.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
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.
Identifiants
pubmed: 39456084
doi: 10.1186/s13005-024-00466-6
pii: 10.1186/s13005-024-00466-6
doi:
Substances chimiques
Amphiregulin
0
ErbB Receptors
EC 2.7.10.1
AREG protein, human
0
EGFR protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
62Subventions
Organisme : the National Natural Science Foundation of China (NSFC) grants
ID : 82101186
Organisme : the National Natural Science Foundation of China (NSFC) grants
ID : 82303870
Organisme : the National Natural Science Foundation of China (NSFC) grants
ID : 81900918
Organisme : Guangdong Natural Science Foundation of China grants
ID : 2021A1515011127
Organisme : Guangdong Natural Science Foundation of China grants
ID : 2022A1515010002
Organisme : Guangzhou Science and Technology Plan Project
ID : 2024A04J4630
Organisme : Key Clinical Technique of Guangzhou
ID : 2023P-ZD06
Informations de copyright
© 2024. The Author(s).
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