We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
RelB upregulates PD-L1 and exacerbates prostate cancer immune evasion.
- Authors
Zhang, Yanyan; Zhu, Shuyi; Du, Yuanyuan; Xu, Fan; Sun, Wenbo; Xu, Zhi; Wang, Xiumei; Qian, Peipei; Zhang, Qin; Feng, Jifeng; Xu, Yong
- Abstract
Background : The interaction between programmed death receptor (PD-1) and its ligand (PD-L1) is essential for suppressing activated T-lymphocytes. However, the precise mechanisms underlying PD-L1 overexpression in tumours have yet to be fully elucidated. Here, we describe that RelB participates in the immune evasion of prostate cancer (PCa) via cis/trans transcriptional upregulation of PD-L1. Methods : Based on transcriptome results, RelB was manipulated in multiple human and murine PCa cell lines. Activated CD4+ and CD8+ T cells were cocultured with PCa cells with different levels of RelB to examine the effect of tumourous RelB on T cell immunity. Male mice were injected with murine PCa cells to validate the effect of RelB on the PD-1/PD-L1-mediated immune checkpoint using both tumour growth and metastatic experimental models. Results : PD-L1 is uniquely expressed at a high level in PCa with high constitutive RelB and correlates with the patients' Gleason scores. Indeed, a high level of PD-L1 is associated with RelB nuclear translocation in AR-negative aggressive PCa cells. Conversely, the silencing of RelB in advanced PCa cells resulted in reduced PD-L1 expression and enhanced susceptibility of PCa cells to the T cell immune response in vitro and in vivo. Mechanistically, a proximal NF-κB enhancer element was identified in the core promoter region of the human CD274 gene, which is responsible for RelB-mediated PD-L1 transcriptional activation. This finding provides an informative insight into immune checkpoint blockade by administering RelB within the tumour microenvironment. Conclusion : This study deciphers the molecular mechanism by which tumourous RelB contributes to immune evasion by inhibiting T cell immunity via the amplification of the PD-L1/PD-1-mediated immune checkpoint.
- Subjects
PROGRAMMED death-ligand 1; IMMUNE checkpoint proteins; PROSTATE cancer; T cells; DEATH receptors
- Publication
Journal of Experimental & Clinical Cancer Research (17569966), 2022, Vol 41, Issue 1, p1
- ISSN
1756-9966
- Publication type
Article
- DOI
10.1186/s13046-022-02243-2