Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.
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Abstract | The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined HNSCC subtypes by their malignant and stromal composition and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis. |
Year of Publication | 2017
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Journal | Cell
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Volume | 171
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Issue | 7
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Pages | 1611-1624.e24
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Date Published | 2017 Dec 14
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ISSN | 1097-4172
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DOI | 10.1016/j.cell.2017.10.044
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PubMed ID | 29198524
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PubMed Central ID | PMC5878932
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Grant list | DP1 CA216873 / CA / NCI NIH HHS / United States
U24 CA180922 / CA / NCI NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
R01 DE022087 / DE / NIDCR NIH HHS / United States
R33 CA202820 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States
P30 CA016058 / CA / NCI NIH HHS / United States
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