Dataset Information

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

ABSTRACT: Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8⁺ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3⁺ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

SUBMITTER: Peng WS

PROVIDER: S-EPMC8794254 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

Peng Wen-Sa WS Zhou Xin X Yan Wen-Bin WB Li Yu-Jiao YJ Du Cheng-Run CR Wang Xiao-Shen XS Shen Chun-Ying CY Wang Qi-Feng QF Ying Hong-Mei HM Lu Xue-Guan XG Xu Ting-Ting TT Hu Chao-Su CS

Oncoimmunology 20220125 1

Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural ...[more]

PMID: 35096485

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Project description:BackgroundPrimary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the intratumoural heterogeneity and TME diversity of PCAS using single-cell RNA sequencing (scRNA-seq).MethodsWe performed scRNA-seq analysis on tumour samples from four patients with PCAS, supplemented with multicolour immunohistochemistry for identification. We used scRNA-seq data from five normal cardiac tissue samples downloaded from public databases for comparative analyses. Bioinformatic analyses, including Cell Ranger, Seurat, Monocle2, hdWGCNA, SCENIC and NicheNet, were utilized to identify distinct cell populations, transcriptional patterns, and co-regulating gene modules.ResultsOur analysis revealed significant intratumoural heterogeneity in PCAS driven by diverse biological processes such as protein synthesis, degradation, and RIG-I signalling inhibition. The SCENIC analysis identified three primary transcription factors' clusters (CEBPB, MYC and TAL1). T-cell subset analysis showed exhausted antigen-specific T-cells, complicating the efficacy of immune checkpoint blockade. Furthermore, we observed suppressive macrophages (SPP1+ and OLR1+) and reduced mitochondrial gene MT-RNR2 (MTRNR2L12) expression in TME-infiltrating cells, indicating impaired mitochondrial function.ConclusionThis study elucidates the complex cellular landscape and immune microenvironment of PCAS, highlighting potential molecular targets for the development of novel therapies. These findings underscore the importance of a multifaceted therapeutic approach for addressing the challenges posed by PCAS's heterogeneity and immune evasion.Key pointsInsights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities. Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages). Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting.

Dataset Information

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

Publications

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

Similar Datasets

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