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Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7854640 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.

Liu Yang Y He Shuai S Wang Xi-Liang XL Peng Wan W Chen Qiu-Yan QY Chi Dong-Mei DM Chen Jie-Rong JR Han Bo-Wei BW Lin Guo-Wang GW Li Yi-Qi YQ Wang Qian-Yu QY Peng Rou-Jun RJ Wei Pan-Pan PP Guo Xiang X Li Bo B Xia Xiaojun X Mai Hai-Qiang HQ Hu Xue-Da XD Zhang Zemin Z Zeng Yi-Xin YX Bei Jin-Xin JX

Nature communications 20210202 1

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<sup>+</sup> T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Tr ...[more]

PMID: 33531485

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Project description:BackgroundHigh throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms.MethodsUsing the Chromium 10X platform, we sequenced a total of ~ 120,000 cells from fresh and cryopreserved replicates across three primary breast cancers, two primary prostate cancers and a cutaneous melanoma. We performed detailed analyses between cells from each condition to assess the effects of cryopreservation on cellular heterogeneity, cell quality, clustering and the identification of gene ontologies. In addition, we performed single-cell immunophenotyping using CITE-Seq on a single breast cancer sample cryopreserved as solid tissue fragments.ResultsTumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on the results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for detecting cell-surface proteins using CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing.ConclusionsWe show that the viable cryopreservation of human cancers provides high-quality single-cells for multi-omics analysis. Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies.

Dataset Information

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.

Publications

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.

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