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Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression

Nasopharyngeal carcinoma (NPC), featured by Epstein-Barr virus (EBV) infection and regional epidemiology, is curable when detected early, but highly lethal at an advanced stage. The molecular mechanism of NPC progression toward a clinically uncontrollable stage remains elusive. In this study, we dev...

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Autores principales: Shi, Xiaojie, Pan, Junyan, Qiu, Fufang, Wu, Liqin, Zhang, Xuyan, Feng, Yan, Gu, Xiaoyi, Zhao, Jikuang, Zheng, Wenwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011158/
https://www.ncbi.nlm.nih.gov/pubmed/35433690
http://dx.doi.org/10.3389/fcell.2022.857137
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author Shi, Xiaojie
Pan, Junyan
Qiu, Fufang
Wu, Liqin
Zhang, Xuyan
Feng, Yan
Gu, Xiaoyi
Zhao, Jikuang
Zheng, Wenwei
author_facet Shi, Xiaojie
Pan, Junyan
Qiu, Fufang
Wu, Liqin
Zhang, Xuyan
Feng, Yan
Gu, Xiaoyi
Zhao, Jikuang
Zheng, Wenwei
author_sort Shi, Xiaojie
collection PubMed
description Nasopharyngeal carcinoma (NPC), featured by Epstein-Barr virus (EBV) infection and regional epidemiology, is curable when detected early, but highly lethal at an advanced stage. The molecular mechanism of NPC progression toward a clinically uncontrollable stage remains elusive. In this study, we developed a novel computational framework to conduct multiscale transcriptomic analysis during NPC progression. The framework consists of four modules enabling transcriptomic analyses spanning from single-cell, bulk, microenvironment, to cohort scales. The bulk-transcriptomic analysis of 133 NPC or normal samples unraveled leading functional enrichments of cell-cycle acceleration, epithelial-mesenchymal transition, and chemokine-modulated inflammatory response during NPC progression. The chemokine CXCL10 in the NPC microenvironment, discovered by single-cell RNA sequencing data analysis, recruits cytotoxic T cells through interacting with its receptor CXCR3 at early but late stages. This T-cell mistrafficking was featured by the decline of cytotoxic T cells and the increase of regulatory T cells, accompanied with B-cell depletion confirmed by immunohistochemistry staining. The featured immunomodulatory chemokines were commonly upregulated in the majority of cancers associated with viral or bacterial infections.
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spelling pubmed-90111582022-04-16 Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression Shi, Xiaojie Pan, Junyan Qiu, Fufang Wu, Liqin Zhang, Xuyan Feng, Yan Gu, Xiaoyi Zhao, Jikuang Zheng, Wenwei Front Cell Dev Biol Cell and Developmental Biology Nasopharyngeal carcinoma (NPC), featured by Epstein-Barr virus (EBV) infection and regional epidemiology, is curable when detected early, but highly lethal at an advanced stage. The molecular mechanism of NPC progression toward a clinically uncontrollable stage remains elusive. In this study, we developed a novel computational framework to conduct multiscale transcriptomic analysis during NPC progression. The framework consists of four modules enabling transcriptomic analyses spanning from single-cell, bulk, microenvironment, to cohort scales. The bulk-transcriptomic analysis of 133 NPC or normal samples unraveled leading functional enrichments of cell-cycle acceleration, epithelial-mesenchymal transition, and chemokine-modulated inflammatory response during NPC progression. The chemokine CXCL10 in the NPC microenvironment, discovered by single-cell RNA sequencing data analysis, recruits cytotoxic T cells through interacting with its receptor CXCR3 at early but late stages. This T-cell mistrafficking was featured by the decline of cytotoxic T cells and the increase of regulatory T cells, accompanied with B-cell depletion confirmed by immunohistochemistry staining. The featured immunomodulatory chemokines were commonly upregulated in the majority of cancers associated with viral or bacterial infections. Frontiers Media S.A. 2022-04-01 /pmc/articles/PMC9011158/ /pubmed/35433690 http://dx.doi.org/10.3389/fcell.2022.857137 Text en Copyright © 2022 Shi, Pan, Qiu, Wu, Zhang, Feng, Gu, Zhao and Zheng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Shi, Xiaojie
Pan, Junyan
Qiu, Fufang
Wu, Liqin
Zhang, Xuyan
Feng, Yan
Gu, Xiaoyi
Zhao, Jikuang
Zheng, Wenwei
Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression
title Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression
title_full Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression
title_fullStr Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression
title_full_unstemmed Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression
title_short Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression
title_sort multiscale transcriptomic integration reveals b-cell depletion and t-cell mistrafficking in nasopharyngeal carcinoma progression
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011158/
https://www.ncbi.nlm.nih.gov/pubmed/35433690
http://dx.doi.org/10.3389/fcell.2022.857137
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