Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma

Gong, Lanqi; Kwong, Dora Lai-Wan; Dai, Wei; Wu, Pingan; Li, Shanshan; Yan, Qian; Zhang, Yu; Zhang, Baifeng; Fang, Xiaona; Liu, Li; Luo, Min; Liu, Beilei; Chow, Larry Ka-Yue; Chen, Qing‐Yun; Huang, Jinlin; Lee, Victor; Lam, Ka-On; Lo, Anthony W.I.; Chen, Zhiwei; Wang, Yan; Lee, Anne W.M.; Guan, Xin‐Yuan

doi:10.1038/s41467-021-21795-z

Cited by 96 publications

(111 citation statements)

References 52 publications

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“…S15c ). We found HLA-DRA, as an exhaustion marker, expressed in CD8 + T cells 50 . IL32 showed higher expression in CD4 + T and Treg cells, which was previously reported to be associated with immune suppression 51 .…”

Section: Resultsmentioning

confidence: 72%

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

Wang

Zhou

et al. 2021

Nat Commun

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Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis.

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Section: Resultsmentioning

confidence: 72%

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

Wang

Zhou

et al. 2021

Nat Commun

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“…NPC is categorized as an inflamed tumor based on its spatial localization of stromal cells with respect to tumor compartments (22). Stromal cells are in close proximity to and in contact with NPC cells, instead of being embedded in the surrounding regions away from the tumor core.…”

Section: The Heterogenous Npc Microenvironment Shaped By Locoregional Lymphoid Infiltration Ebv Infection and Tumor-mediated Recruitmentmentioning

confidence: 99%

The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment

et al. 2021

Self Cite

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The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.

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“…5 C,D). On the other hand, clusters 2 and 3, in 4T1 and EMT6 respectively, had a similar transcriptional profile attributable to a proliferative B cell population, as confirmed by the expression of Mki67 and Mcm5 genes 44,62 . Similarly, cluster 4 and cluster 7, in 4T1 and EMT6 respectively, highly expressed Cd38 gene but not Mki67 (Fig.…”

Section: Common B Cell Sub-cluster Proportions On Both the Cell Line Tmesmentioning

confidence: 77%

A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies

Carpen

Falvo

Orecchioni

et al. 2021

Preprint

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Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as anti-PD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.Here, an assessment of the immune landscape in the tumour microenvironment (TME) of two TNBC mouse models (4T1 and EMT6 cell lines) has been performed using single-cell RNA sequencing (scRNA-seq) technology. Specifically, immune cells were evaluated in untreated conditions and after being treated with chemotherapy or immunotherapy used as single agents or in combination. A decrease of regulatory T cells, compared to the untreated TME, was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy; on the other hand, an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were found enriched in treatments with low efficacy while opposite behaviour was associated with M1-like macrophages. For both cell lines, similar proportions of B cells were detected with an increase of proliferative B cells in treatments that involved cisplatin in combination with anti-PD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC for a possible application at the clinical level.

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Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma

Cited by 96 publications

References 52 publications

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment

A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies

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