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Published in: BMC Cancer 1/2022

Open Access 01-12-2022 | Epstein-Barr Virus | Research article

Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer

Authors: Soehartati A. Gondhowiardjo, Marlinda Adham, Lisnawati Rachmadi, Tubagus Djumhana Atmakusuma, Demak Lumban Tobing, Mahesa Auzan, Agustinus Darmadi Hariyanto, Dede Sulaeman, Tiara Bunga Mayang Permata, Handoko

Published in: BMC Cancer | Issue 1/2022

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Abstract

Introduction

EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression.

Method

Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out.

Result

Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value < 0.001) between CD8 and GTVp. There was also moderate correlation (ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn.

Discussion

We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system.
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Metadata
Title
Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer
Authors
Soehartati A. Gondhowiardjo
Marlinda Adham
Lisnawati Rachmadi
Tubagus Djumhana Atmakusuma
Demak Lumban Tobing
Mahesa Auzan
Agustinus Darmadi Hariyanto
Dede Sulaeman
Tiara Bunga Mayang Permata
Handoko
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2022
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-022-09948-9

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