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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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 |
Sumario: | 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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