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CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma

BACKGROUND: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cance...

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Autores principales: Al-Rajhi, Nasser, Soudy, Hussein, Ahmed, Shoaib A., Elhassan, Tusneem, Mohammed, Shamayel F., Khoja, Hatim A., Ghebeh, Hazem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227256/
https://www.ncbi.nlm.nih.gov/pubmed/32199452
http://dx.doi.org/10.1186/s12885-020-06757-w
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author Al-Rajhi, Nasser
Soudy, Hussein
Ahmed, Shoaib A.
Elhassan, Tusneem
Mohammed, Shamayel F.
Khoja, Hatim A.
Ghebeh, Hazem
author_facet Al-Rajhi, Nasser
Soudy, Hussein
Ahmed, Shoaib A.
Elhassan, Tusneem
Mohammed, Shamayel F.
Khoja, Hatim A.
Ghebeh, Hazem
author_sort Al-Rajhi, Nasser
collection PubMed
description BACKGROUND: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. METHODS: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. RESULTS: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). CONCLUSIONS: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.
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spelling pubmed-72272562020-05-27 CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma Al-Rajhi, Nasser Soudy, Hussein Ahmed, Shoaib A. Elhassan, Tusneem Mohammed, Shamayel F. Khoja, Hatim A. Ghebeh, Hazem BMC Cancer Research Article BACKGROUND: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. METHODS: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. RESULTS: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). CONCLUSIONS: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials. BioMed Central 2020-03-21 /pmc/articles/PMC7227256/ /pubmed/32199452 http://dx.doi.org/10.1186/s12885-020-06757-w Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://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
Al-Rajhi, Nasser
Soudy, Hussein
Ahmed, Shoaib A.
Elhassan, Tusneem
Mohammed, Shamayel F.
Khoja, Hatim A.
Ghebeh, Hazem
CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
title CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
title_full CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
title_fullStr CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
title_full_unstemmed CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
title_short CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
title_sort cd3+t-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227256/
https://www.ncbi.nlm.nih.gov/pubmed/32199452
http://dx.doi.org/10.1186/s12885-020-06757-w
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