PMID- 34988205
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220429
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 22
DP  - 2021 Nov
TI  - Growth hormone secretagogue receptor deficiency promotes lung cancer growth by 
      affecting the Th17/Treg balance.
PG  - 1696
LID - 10.21037/atm-21-5727 [doi]
LID - 1696
AB  - BACKGROUND: Cluster of differentiation 4 (CD4(+)) T cells plays a prominent role 
      in eliminating cancer cells. The balance between T helper (Th)17 and regulatory T 
      (Treg) cells is crucial for optimal immune response and protection against 
      cancer. Growth hormone secretagogue receptor 1a (GHSR1a), a member of the G 
      protein-coupled protein receptor superfamily, plays a critical role in immune 
      cell function. The aim of our study is to investigate the role of GHSR1a in 
      CD4(+) T cell differentiation and lung cancer progression. METHODS: A 
      subcutaneous lung cancer model was used to examine the role of GHSR1a in 
      controlling tumor growth. Lewis lung carcinoma (LLC) cells were subcutaneously 
      implanted into Ghsr1a (-/-) mice and wild-type (WT) mice. The ratio of Th17 and 
      Treg in the draining lymph node of Ghsr1a (-/-) mice and WT tumor-bearing mice 
      was detected by fluorescence-activated cell sorting (FACS). The effect of GHSR1a 
      deficiency on Th17 and Treg cell differentiation was examined using an in vitro 
      differentiation assay. The phosphorylation of mammalian target of rapamycin 
      (mTOR), signal transducer, and activator of transcription (STAT)3 and STAT5 
      signaling was detected with Western blot. RESULTS: We found that the ablation of 
      GHSR1a resulted in impaired anti-tumor immunity to control lung cancer growth in 
      vivo. We also demonstrated that the deficiency of GHSR1a promoted a shift in the 
      Th17/Treg balance toward enhanced Treg differentiation and inhibited Th17 
      differentiation both in vivo and in vitro, which suggests that GHSR1a regulates T 
      cell lineage choices between Th17 and Treg cell commitment in the tumor 
      microenvironment. Mechanistically, the deficiency of GHSR1a resulted in reduced 
      phosphorylation in mTOR and STAT3, and increased phosphorylation in STAT5. 
      CONCLUSIONS: Our findings showed the important role of GHSR1a in CD4(+) T cell 
      differentiation in the context of the lung cancer microenvironment. This research 
      provides a novel molecular target and insights into interventions for the 
      prevention and treatment of lung cancer.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Wu, Liang
AU  - Wu L
AD  - Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Li, Dongliang
AU  - Li D
AD  - Department of Thoracic Surgery, Shanxi Provincial Tumor Hospital, Taiyuan, China.
FAU - Qin, Linlin
AU  - Qin L
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Wang, Qingliang
AU  - Wang Q
AD  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Saito, Yuichi
AU  - Saito Y
AD  - Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
FAU - Sara, Ricciardi
AU  - Sara R
AD  - Division of Thoracic Surgery, IRCCS University Hospital of Bologna, Bologna, 
      Italy.
FAU - Fan, Jiang
AU  - Fan J
AD  - Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8667136
OTO - NOTNLM
OT  - Growth hormone secretagogue receptor 1a (GHSR1a)
OT  - Th17/Treg balance
OT  - lung cancer
OT  - microenvironment
OT  - tumor immunity
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-5727). The authors have no 
      conflicts of interest to declare.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/07 06:01
PMCR- 2021/11/01
CRDT- 2022/01/06 06:00
PHST- 2020/12/22 00:00 [received]
PHST- 2021/11/19 00:00 [accepted]
PHST- 2022/01/06 06:00 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/07 06:01 [medline]
PHST- 2021/11/01 00:00 [pmc-release]
AID - atm-09-22-1696 [pii]
AID - 10.21037/atm-21-5727 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Nov;9(22):1696. doi: 10.21037/atm-21-5727.