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High MHC-II expression in Epstein–Barr virus-associated gastric cancers suggests that tumor cells serve an important role in antigen presentation.
- Source :
- Scientific Reports; 9/8/2020, Vol. 10 Issue 1, pN.PAG-N.PAG, 1p
- Publication Year :
- 2020
-
Abstract
- EBV-associated gastric adenocarcinomas (EBVaGCs) often exhibit better clinical outcomes than EBV negative gastric cancers (GCs), which could be related to their consistent expression of foreign viral antigens. Antigen-presenting cells (APCs) present peptide antigens in the context of the class-II major histocompatibility complex (MHC-II). During inflammatory conditions, epithelial cells express MHC-II and function as accessory APCs. Utilizing RNA-seq data from nearly 400 GC patients, we determined the impact of EBV-status on expression of MHC-II components, genes involved in their regulation, and T-cell co-stimulation. Virtually all MHC-II genes were significantly upregulated in EBVaGCs compared to normal tissues, or other GC subtypes. Genes involved in antigen presentation were also significantly upregulated in EBVaGCs, as were the key MHC-II transcriptional regulators CIITA and RFX5. This was unexpected as the EBV encoded BZLF1 protein can repress CIITA transcription and is expressed in many EBVaGCs. Furthermore, MHC-II upregulation was strongly correlated with elevated intratumoral levels of interferon-gamma. In addition, expression of co-stimulatory molecules involved in T-cell activation and survival was also significantly increased in EBVaGCs. Thus, gastric adenocarcinoma cells may functionally contribute to the highly immunogenic tumor microenvironment observed in EBVaGCs via a previously unappreciated role in interferon-induced antigen presentation. [ABSTRACT FROM AUTHOR]
- Subjects :
- EPSTEIN-Barr virus
STOMACH cancer
CANCER cells
ANTIGENS
T cells
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- 145625892
- Full Text :
- https://doi.org/10.1038/s41598-020-71775-4