Exosomes from salivary adenoid cystic carcinoma promote the expression of PD-L1 in fibroblasts
10.3872/j.issn.1007-385x.2020.03.005
- VernacularTitle:涎腺腺样囊性癌来源外泌体促进成纤维细胞PD-L1表达
- Author:
ZHENG Xing
1
;
XU Zhengli
2
Author Information
1. Department of Stomatology, the Third Affiliated Hospital of Naval Medical University
2. Departments of Stomatology, the FirstAffiliated Hospital of Naval Medical University,
- Publication Type:Journal Article
- Keywords:
salivary adenoid cystic carcinoma (SACC);
SACC-83 cell;
cancer-related fibroblast;
HPLF cell;
exosome;
PD-L1
- From:
Chinese Journal of Cancer Biotherapy
2020;27(3):242-247
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of salivary adenoid cystic carcinoma (SACC) derived exosomes on PD-L1 expression in fibroblasts. Methods: Exosomes of SACC-83 cell line were extracted by exosome isolation kit, and its particle size, density and phenotypes were identified by electron microscope.After being labeled with PKH67 fluorescence, exosomes were co-incubated with HPLF to observe whether the exosomes could be ingested by fibroblasts under confocal microscope. After co-incubation with the exosomes, the differentially expressed genes (DEGs) in HPLF cells were detected by whole transcriptome sequencing. GO analysis together with KEGG enrichment analysis was used to clarify the biological functions and related signaling pathways related with the DEGs. qPCR, Western blotting and Flow cytometry were used to detect the effect of tumor exosomes on the mRNAand protein expressions of PD-L1, LAG3 and IDO1 in HPLF fibroblasts. Results: SACC exosomes specifically expressed CD63, CD81 and TSG101 molecules, and could be ingested by fibroblasts. After the treatment of fibroblasts by exosomes, the expression of PD-L1 molecule was significantly up-regulated (Fold change=10.19), and the DEGs were significantly enriched in the immune response signaling pathways, such as TNF, NF-κB and cGAS-String pathway, etc. In vitro experiments showed that exosomes could significantly promote the expression of PD-L1 in HPLF cells at both mRNA and protein levels (24.7±4.75 vs 1.03±0.11,P<0.05). Conclusion: Exosomes of SACC can promote the expression of immunocheckpoint ligand PD-L1 in fibroblasts.
- Full text:20200305.pdf
