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Cell. 2017 Dec 14;171(7):1611-1624.e24. doi: 10.1016/j.cell.2017.10.044. Epub 2017 Nov 30.

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.

Author information

1
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA.
2
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: itay.tirosh@weizmann.ac.il.
3
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
4
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
5
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
6
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
7
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA; Department of Otolaryngology, Ohio State University, Columbus, OH 43210, USA.
8
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA.
9
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: derrick_lin@meei.harvard.edu.
10
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biology and Koch Institute, MIT, Boston, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: aregev@broadinstitute.org.
11
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: bernstein.bradley@mgh.harvard.edu.

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.

KEYWORDS:

epithelial-to-mesenchymal transition; head and neck squamous cell carcinoma; intra-tumoral heterogeneity; metastasis; scRNA-seq; single-cell RNA sequencing; tumor microenvironment

PMID:
29198524
PMCID:
PMC5878932
DOI:
10.1016/j.cell.2017.10.044
[Indexed for MEDLINE]
Free PMC Article

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