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Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375267/ https://www.ncbi.nlm.nih.gov/pubmed/35963999 http://dx.doi.org/10.1186/s12885-022-09948-9 |
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author | Gondhowiardjo, Soehartati A. Adham, Marlinda Rachmadi, Lisnawati Atmakusuma, Tubagus Djumhana Tobing, Demak Lumban Auzan, Mahesa Hariyanto, Agustinus Darmadi Sulaeman, Dede Permata, Tiara Bunga Mayang Handoko |
author_facet | Gondhowiardjo, Soehartati A. Adham, Marlinda Rachmadi, Lisnawati Atmakusuma, Tubagus Djumhana Tobing, Demak Lumban Auzan, Mahesa Hariyanto, Agustinus Darmadi Sulaeman, Dede Permata, Tiara Bunga Mayang Handoko |
author_sort | Gondhowiardjo, Soehartati A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9375267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93752672022-08-14 Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer Gondhowiardjo, Soehartati A. Adham, Marlinda Rachmadi, Lisnawati Atmakusuma, Tubagus Djumhana Tobing, Demak Lumban Auzan, Mahesa Hariyanto, Agustinus Darmadi Sulaeman, Dede Permata, Tiara Bunga Mayang Handoko BMC Cancer Research Article 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. BioMed Central 2022-08-13 /pmc/articles/PMC9375267/ /pubmed/35963999 http://dx.doi.org/10.1186/s12885-022-09948-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Gondhowiardjo, Soehartati A. Adham, Marlinda Rachmadi, Lisnawati Atmakusuma, Tubagus Djumhana Tobing, Demak Lumban Auzan, Mahesa Hariyanto, Agustinus Darmadi Sulaeman, Dede Permata, Tiara Bunga Mayang Handoko Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer |
title | Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer |
title_full | Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer |
title_fullStr | Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer |
title_full_unstemmed | Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer |
title_short | Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer |
title_sort | immune cells markers within local tumor microenvironment are associated with ebv oncoprotein in nasopharyngeal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375267/ https://www.ncbi.nlm.nih.gov/pubmed/35963999 http://dx.doi.org/10.1186/s12885-022-09948-9 |
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