Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer
Few studies have reported whether nutrients in the tumor microenvironment can regulate the expression of PD-L1. Since tumor cells are often situated in a low-glutamine environment, we investigated PD-L1 expression under glutamine deprivation in bladder cancer cells. PD-L1 expression and the activati...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:576a3ea6d50b43ddad717dce479a33b92021-11-05T12:35:19ZImmunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer2296-889X10.3389/fmolb.2021.687305https://doaj.org/article/576a3ea6d50b43ddad717dce479a33b92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.687305/fullhttps://doaj.org/toc/2296-889XFew studies have reported whether nutrients in the tumor microenvironment can regulate the expression of PD-L1. Since tumor cells are often situated in a low-glutamine environment, we investigated PD-L1 expression under glutamine deprivation in bladder cancer cells. PD-L1 expression and the activation of the EGFR/MEK/ERK/c-Jun signaling pathway under glutamine deprivation were investigated by qPCR, Western blot, and immunofluorescence analyses. C-Jun-mediated transcriptional regulation of the PD-L1 gene was assessed by ChIP. PD-L1 expression and activation of the EGFR/MEK/ERK/c-Jun signaling pathway were assessed in T24 cells, TCCSUP cells and BALB/c mice with or without glutamine supplementation. Additionally, the impact of PD-L1 expression under glutamine deprivation on the function of T cells was investigated by ELISA. The expression of PD-L1 and EGFR/MEK/ERK/c-Jun pathway activation were elevated by glutamine deprivation, and c-Jun was enriched in the enhancer region of PD-L1. The expression of PD-L1 was considerably impaired by inhibiting the EGFR/MEK/ERK/c-Jun pathway and was elevated by activating this signaling pathway. In addition, the elevated PD-L1 expression and MEK/ERK/c-Jun signaling pathway activation were reduced by glutamine supplementation in vitro and in vivo. PD-L1 upregulation by glutamine deprivation in bladder cancer cells could reduce IFN-γ production by T cells. The expression of PD-L1 was upregulated under glutamine deprivation through the EGFR/MEK/ERK/c-Jun pathway to impair T cell function.Liping WangTing XuXuecheng YangZhijuan LiangJisheng ZhangDan LiYuanbin ChenGuofeng MaYonghua WangYonghua WangYe LiangHaitao NiuHaitao NiuFrontiers Media S.A.articleglutamine deprivationPD-L1bladder cancerT cellsMEK/ERK/c-Jun signaling pathwayBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021) |
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| topic |
glutamine deprivation PD-L1 bladder cancer T cells MEK/ERK/c-Jun signaling pathway Biology (General) QH301-705.5 |
| spellingShingle |
glutamine deprivation PD-L1 bladder cancer T cells MEK/ERK/c-Jun signaling pathway Biology (General) QH301-705.5 Liping Wang Ting Xu Xuecheng Yang Zhijuan Liang Jisheng Zhang Dan Li Yuanbin Chen Guofeng Ma Yonghua Wang Yonghua Wang Ye Liang Haitao Niu Haitao Niu Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer |
| description |
Few studies have reported whether nutrients in the tumor microenvironment can regulate the expression of PD-L1. Since tumor cells are often situated in a low-glutamine environment, we investigated PD-L1 expression under glutamine deprivation in bladder cancer cells. PD-L1 expression and the activation of the EGFR/MEK/ERK/c-Jun signaling pathway under glutamine deprivation were investigated by qPCR, Western blot, and immunofluorescence analyses. C-Jun-mediated transcriptional regulation of the PD-L1 gene was assessed by ChIP. PD-L1 expression and activation of the EGFR/MEK/ERK/c-Jun signaling pathway were assessed in T24 cells, TCCSUP cells and BALB/c mice with or without glutamine supplementation. Additionally, the impact of PD-L1 expression under glutamine deprivation on the function of T cells was investigated by ELISA. The expression of PD-L1 and EGFR/MEK/ERK/c-Jun pathway activation were elevated by glutamine deprivation, and c-Jun was enriched in the enhancer region of PD-L1. The expression of PD-L1 was considerably impaired by inhibiting the EGFR/MEK/ERK/c-Jun pathway and was elevated by activating this signaling pathway. In addition, the elevated PD-L1 expression and MEK/ERK/c-Jun signaling pathway activation were reduced by glutamine supplementation in vitro and in vivo. PD-L1 upregulation by glutamine deprivation in bladder cancer cells could reduce IFN-γ production by T cells. The expression of PD-L1 was upregulated under glutamine deprivation through the EGFR/MEK/ERK/c-Jun pathway to impair T cell function. |
| format |
article |
| author |
Liping Wang Ting Xu Xuecheng Yang Zhijuan Liang Jisheng Zhang Dan Li Yuanbin Chen Guofeng Ma Yonghua Wang Yonghua Wang Ye Liang Haitao Niu Haitao Niu |
| author_facet |
Liping Wang Ting Xu Xuecheng Yang Zhijuan Liang Jisheng Zhang Dan Li Yuanbin Chen Guofeng Ma Yonghua Wang Yonghua Wang Ye Liang Haitao Niu Haitao Niu |
| author_sort |
Liping Wang |
| title |
Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer |
| title_short |
Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer |
| title_full |
Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer |
| title_fullStr |
Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer |
| title_full_unstemmed |
Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer |
| title_sort |
immunosuppression induced by glutamine deprivation occurs via activating pd-l1 transcription in bladder cancer |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/576a3ea6d50b43ddad717dce479a33b9 |
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