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Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

SIMPLE SUMMARY: The post-radiotherapy (RT) clearance of tumor-derived plasma EBV DNA is associated with a better prognosis in patients with nasopharyngeal cancer (NPC). T cells may play a critical role in the clearance of plasma EBV DNA in NPC. We explored the dynamic changes in circulating T-cell p...

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Autores principales: Mahajan, Shweta, Balcioglu, Hayri E., Oostvogels, Astrid, Dik, Willem A., Chan, K. C. Allen, Lo, Kwok-Wai, Hui, Edwin P., Tsang, Anna, Tong, Joanna, Lam, Wai Kei Jacky, Wong, Kenneth, Chan, Anthony T. C., Ma, Brigette B. Y., Debets, Reno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047204/
https://www.ncbi.nlm.nih.gov/pubmed/36980772
http://dx.doi.org/10.3390/cancers15061887
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author Mahajan, Shweta
Balcioglu, Hayri E.
Oostvogels, Astrid
Dik, Willem A.
Chan, K. C. Allen
Lo, Kwok-Wai
Hui, Edwin P.
Tsang, Anna
Tong, Joanna
Lam, Wai Kei Jacky
Wong, Kenneth
Chan, Anthony T. C.
Ma, Brigette B. Y.
Debets, Reno
author_facet Mahajan, Shweta
Balcioglu, Hayri E.
Oostvogels, Astrid
Dik, Willem A.
Chan, K. C. Allen
Lo, Kwok-Wai
Hui, Edwin P.
Tsang, Anna
Tong, Joanna
Lam, Wai Kei Jacky
Wong, Kenneth
Chan, Anthony T. C.
Ma, Brigette B. Y.
Debets, Reno
author_sort Mahajan, Shweta
collection PubMed
description SIMPLE SUMMARY: The post-radiotherapy (RT) clearance of tumor-derived plasma EBV DNA is associated with a better prognosis in patients with nasopharyngeal cancer (NPC). T cells may play a critical role in the clearance of plasma EBV DNA in NPC. We explored the dynamic changes in circulating T-cell profiles during RT and observed that a temporal increase in the frequency of CD8+ T cells expressing CCR1, 4 and/or 5 was associated with plasma EBV DNA clearance. Moreover, differences in the plasma levels of the corresponding chemo-attractants are related to clinical outcome. Our study demonstrated correlation between plasma EBV DNA clearance post-RT and T-cell chemotaxis, which requires validation in larger cohorts. Markers of T-cell chemotaxis may be prognostic biomarkers in patients with NPC undergoing RT. ABSTRACT: Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.
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spelling pubmed-100472042023-03-29 Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy Mahajan, Shweta Balcioglu, Hayri E. Oostvogels, Astrid Dik, Willem A. Chan, K. C. Allen Lo, Kwok-Wai Hui, Edwin P. Tsang, Anna Tong, Joanna Lam, Wai Kei Jacky Wong, Kenneth Chan, Anthony T. C. Ma, Brigette B. Y. Debets, Reno Cancers (Basel) Article SIMPLE SUMMARY: The post-radiotherapy (RT) clearance of tumor-derived plasma EBV DNA is associated with a better prognosis in patients with nasopharyngeal cancer (NPC). T cells may play a critical role in the clearance of plasma EBV DNA in NPC. We explored the dynamic changes in circulating T-cell profiles during RT and observed that a temporal increase in the frequency of CD8+ T cells expressing CCR1, 4 and/or 5 was associated with plasma EBV DNA clearance. Moreover, differences in the plasma levels of the corresponding chemo-attractants are related to clinical outcome. Our study demonstrated correlation between plasma EBV DNA clearance post-RT and T-cell chemotaxis, which requires validation in larger cohorts. Markers of T-cell chemotaxis may be prognostic biomarkers in patients with NPC undergoing RT. ABSTRACT: Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts. MDPI 2023-03-21 /pmc/articles/PMC10047204/ /pubmed/36980772 http://dx.doi.org/10.3390/cancers15061887 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mahajan, Shweta
Balcioglu, Hayri E.
Oostvogels, Astrid
Dik, Willem A.
Chan, K. C. Allen
Lo, Kwok-Wai
Hui, Edwin P.
Tsang, Anna
Tong, Joanna
Lam, Wai Kei Jacky
Wong, Kenneth
Chan, Anthony T. C.
Ma, Brigette B. Y.
Debets, Reno
Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
title Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
title_full Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
title_fullStr Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
title_full_unstemmed Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
title_short Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
title_sort frequency of peripheral cd8+ t cells expressing chemo-attractant receptors ccr1, 4 and 5 increases in npc patients with ebv clearance upon radiotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047204/
https://www.ncbi.nlm.nih.gov/pubmed/36980772
http://dx.doi.org/10.3390/cancers15061887
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