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单细胞转录组分析揭示了髓源性抑制细胞在头颈部鳞状细胞癌中的临床意义。

Single-cell transcriptome analysis reveals the clinical implications of myeloid-derived suppressor cells in head and neck squamous cell carcinoma.

机构信息

Department of Implant and Prosthodontics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Implant and Prosthodontics, Harbin First Hospital, Harbin, China.

出版信息

Pathol Oncol Res. 2023 Jul 5;29:1611210. doi: 10.3389/pore.2023.1611210. eCollection 2023.

DOI:10.3389/pore.2023.1611210
PMID:37475874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10354270/
Abstract

Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor that arises in the epithelium of the head and neck regions. Myeloid-derived suppressor cells (MDSCs) are one of the tumor-infiltrating immune cell populations, which play a powerful role in inhibiting anti-tumor immune response. Herein, we employed a single-cell RNA sequencing (scRNA-seq) dataset to dissect the heterogeneity of myeloid cells. We found that tumor-associated macrophages (TAMs) and MDSCs were the most abundant myeloid cells in the microenvironment. By cell cluster deconvolution from bulk RNA-seq datasets of larger patient groups, we observed that highly-infiltrated MDSC was a poor prognostic marker for patients' overall survival (OS) probabilities. To better apply the MDSC OS prediction values, we identified a set of six MDSC-related genes (, , , , , and ) as the prognostic signature. In both training and test cohorts, MDSC-related prognostic signature showed a promising value for predicting patients' prognosis outcomes. Further parsing the ligand-receptor pairs of intercellular communications by CellChat, we found that MDSCs could frequently interact with cytotoxic T cells, TAMs, and endothelial cells. These interactions likely contributed to the establishment of an immunosuppressive microenvironment and the promotion of tumor angiogenesis. Our findings suggest that targeting MDSCs may serve as an alternative and promising target for the immunotherapy of HNSC.

摘要

头颈部鳞状细胞癌(HNSC)是最常见的发生于头颈部上皮的恶性肿瘤。髓系来源的抑制细胞(MDSC)是肿瘤浸润免疫细胞群之一,在抑制抗肿瘤免疫反应方面发挥着强大的作用。在此,我们利用单细胞 RNA 测序(scRNA-seq)数据集来剖析髓系细胞的异质性。我们发现肿瘤相关巨噬细胞(TAMs)和 MDSC 是微环境中最丰富的髓系细胞。通过对更大患者群体的批量 RNA-seq 数据集进行细胞聚类反卷积,我们观察到高浸润性 MDSC 是患者总生存(OS)概率的不良预后标志物。为了更好地应用 MDSC OS 预测值,我们确定了一组 6 个 MDSC 相关基因(,,,,,和)作为预后特征。在训练和测试队列中,MDSC 相关的预后特征都显示出了对患者预后结果的良好预测价值。通过 CellChat 进一步解析细胞间通讯的配体-受体对,我们发现 MDSC 可以与细胞毒性 T 细胞、TAMs 和内皮细胞频繁相互作用。这些相互作用可能有助于建立免疫抑制微环境和促进肿瘤血管生成。我们的研究结果表明,针对 MDSC 可能成为 HNSC 免疫治疗的一种替代和有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/401aa54b9551/pore-29-1611210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/886a517a79e4/pore-29-1611210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/47e95957c08c/pore-29-1611210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/0692da26168b/pore-29-1611210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/5136d729c7ea/pore-29-1611210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/401aa54b9551/pore-29-1611210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/886a517a79e4/pore-29-1611210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/47e95957c08c/pore-29-1611210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/0692da26168b/pore-29-1611210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/5136d729c7ea/pore-29-1611210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38a4/10354270/401aa54b9551/pore-29-1611210-g005.jpg

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