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通过单细胞 RNA 测序研究头颈部肿瘤中的免疫和非免疫细胞相互作用。

Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing.

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Nat Commun. 2021 Dec 17;12(1):7338. doi: 10.1038/s41467-021-27619-4.

DOI:10.1038/s41467-021-27619-4
PMID:34921143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8683505/
Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV) and 12 HPV HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.

摘要

头颈部鳞状细胞癌（HNSCC）的特征是肿瘤微环境（TME）中基质细胞、上皮细胞和免疫细胞之间存在复杂的关系。为了开发更有效的治疗方法，我们旨在使用单细胞 RNA 测序研究 6 例人乳头瘤病毒（HPV）和 12 例 HPV HNSCC 患者肿瘤及配对外周血标本中非免疫和免疫细胞群体的异质性、独特细胞群体的特征以及细胞-细胞相互作用。利用这个包含 134606 个细胞的数据集，我们展示了与炎症和 HPV 状态相关的细胞类型特异性特征，描述了在 HPV TME 中具有弹性分化的成纤维细胞的负预后价值，预测了可治疗性靶向检查点受体-配体相互作用，并表明肿瘤相关巨噬细胞是 TME 中 PD-L1 和其他免疫检查点配体的主要贡献者。我们呈现了一个全面的单细胞视角，展示了内在机制和细胞间通讯如何塑造 HNSCC 微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/4cb242e08f39/41467_2021_27619_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/87e5a4b74aab/41467_2021_27619_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/787d8441ddff/41467_2021_27619_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/fa0218cc7f67/41467_2021_27619_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/64dfedc22eb0/41467_2021_27619_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/17ece38189fc/41467_2021_27619_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/1761e69ac525/41467_2021_27619_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/93a4d6b1939f/41467_2021_27619_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/4cb242e08f39/41467_2021_27619_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/87e5a4b74aab/41467_2021_27619_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/787d8441ddff/41467_2021_27619_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/fa0218cc7f67/41467_2021_27619_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/64dfedc22eb0/41467_2021_27619_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/17ece38189fc/41467_2021_27619_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/1761e69ac525/41467_2021_27619_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/93a4d6b1939f/41467_2021_27619_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4a/8683505/4cb242e08f39/41467_2021_27619_Fig8_HTML.jpg

相似文献

[1]
Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing.

Nat Commun. 2021-12-17

[2]
Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma.

Sci Rep. 2021-8-9

[3]
Characterization of the tumor immune microenvironment in human papillomavirus-positive and -negative head and neck squamous cell carcinomas.

Cancer Immunol Immunother. 2021-5

[4]
HPV-positive status associated with inflamed immune microenvironment and improved response to anti-PD-1 therapy in head and neck squamous cell carcinoma.

Sci Rep. 2019-9-16

[5]
Estimation of immune cell content in tumor using single-cell RNA-seq reference data.

BMC Cancer. 2019-7-19

[6]
Morphomolecular analysis of the immune tumor microenvironment in human head and neck cancer.

Cancer Immunol Immunother. 2019-8-23

[7]
HPV16 E5 Mediates Resistance to PD-L1 Blockade and Can Be Targeted with Rimantadine in Head and Neck Cancer.

Cancer Res. 2019-12-17

[8]
Differential Immune Checkpoint Protein Expression in HNSCC: The Role of HGF/MET Signaling.

Int J Mol Sci. 2024-7-4

[9]
Transcriptome analysis reveals the link between lncRNA-mRNA co-expression network and tumor immune microenvironment and overall survival in head and neck squamous cell carcinoma.

BMC Med Genomics. 2020-3-30

[10]
Establishment and validation of immune microenvironmental gene signatures for predicting prognosis in patients with head and neck squamous cell carcinoma.

Int Immunopharmacol. 2021-8

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[2]
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Front Immunol. 2025-8-12

[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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J Transl Med. 2025-7-16

[10]
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本文引用的文献

[1]
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Nat Cancer. 2020-1

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J Clin Oncol. 2019-8-13

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