兰州大学机构库
RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma
Guo, Yanan1; Shen, Rong1; Yang, Keren1; Wang, Yutong1; Song, Haoyun1; Liu, Xiangwen1; Cheng, Xin1; Wu, Rile1; Song, Yanfeng1; Wang, Degui1,2
2023-06-30
Source PublicationCell Death Discovery   Impact Factor & Quartile Of Published Year  The Latest Impact Factor & Quartile
ISSN2058-7716
Volume9Issue:1
page numbers14
AbstractThe failure of melanoma immunotherapy can be mediated by immunosuppression in the tumor microenvironment (TME), and insufficient activation of effector T cells against the tumor. Here, we show that inhibition of galectin-3 (gal-3) enhances the infiltration of T cells in TME and improves the sensitivity of anti-PD-L1 therapy. We identify that RNF8 downregulated the expression of gal-3 by K48-polyubiquitination and promoted gal-3 degradation via the ubiquitin-proteasome system. RNF8 deficiency in the host but sufficiency in implanted melanoma results in immune exclusion and tumor progression due to the upregulation of gal-3. Upregulation of gal-3 decreased the immune cell infiltration by restricting IL-12 and IFN-?. Inhibition of gal-3 reverses immunosuppression and induces immune cell infiltration in the tumor microenvironment. Moreover, gal-3 inhibitor treatment can increase the sensitivity of PD-L1 inhibitors via increasing immune cell infiltration and enhancing immune response in tumors. This study reveals a previously unrecognized immunoregulation function of RNF8 and provides a promising strategy for the therapy of cold tumors. Tremendous effects of melanoma treatment can be achieved by facilitating immune cell infiltration combined with anti-PD-L1 treatment.
PublisherSPRINGERNATURE
DOI10.1038/s41420-023-01500-3
Indexed BySCIE
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:001022405100002
Original Document TypeArticle
PMID 37391451
Citation statistics
Document Type期刊论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/569591
Collection兰州大学
Corresponding AuthorWang, Degui
Affiliation
1.Lanzhou Univ, Sch Basic Med Sci, Lanzhou 73000, Gansu, Peoples R China;
2.NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Peoples R China
Recommended Citation
GB/T 7714
Guo, Yanan,Shen, Rong,Yang, Keren,et al. RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma[J]. Cell Death Discovery,2023,9(1).
APA Guo, Yanan.,Shen, Rong.,Yang, Keren.,Wang, Yutong.,Song, Haoyun.,...&Wang, Degui.(2023).RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma.Cell Death Discovery,9(1).
MLA Guo, Yanan,et al."RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma".Cell Death Discovery 9.1(2023).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[Guo, Yanan]'s Articles
[Shen, Rong]'s Articles
[Yang, Keren]'s Articles
Baidu academic
Similar articles in Baidu academic
[Guo, Yanan]'s Articles
[Shen, Rong]'s Articles
[Yang, Keren]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Guo, Yanan]'s Articles
[Shen, Rong]'s Articles
[Yang, Keren]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.