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Nat Commun ; 12(1): 741, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531485

RESUMO

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.


Assuntos
Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/metabolismo , Microambiente Tumoral/fisiologia , Linfócitos T CD8-Positivos/enzimologia , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral/imunologia
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