Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer
Open accessAbstract
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.
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EMT-like TSK cells lacked expression of classic EMT transcription factors.
“Similar to a previous study of oropharyngeal SCC (Puram et al., 2017), EMT-like TSK cells lacked expression of classic EMT transcription factors (TFs)”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Puram et al., 2017
The Results section (‘A partial EMT program in HNSCC’) reports no detected expression of several classical EMT transcription factors in the source paper’s p-EMT cells. It explicitly identifies an exception: SNAIL2 was detected in 70% of HNSCC cells. The unqualified claim that classic EMT transcription factors were absent omits that exception. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSingle-cell sequencing indicates common traits are preserved across tissues and species.
“While single-cell sequencing indicates common traits are preserved49–51, it will become increasingly pressing to define common and specific effects of CAFs.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [49]
The Results section reports that fibroblast expression states were reproducibly detected across HNSCC tumors. It also describes broad similarity between primary tumors and matched lymph-node metastases, though with differences in fibroblast subsets. These findings support common traits across the studied tumors and sites, but not preservation across species; no page numbers are available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere is a recurrent observation of distinct CAFs exhibiting either a matrix-producing contractile phenotype or an immunomodulating secretome, often termed myoCAFs and iCAFs.
“Nonetheless, there is a recurrent observation of distinct CAFs exhibiting either a matrix-producing contractile phenotype or an immunomodulating secretome — often termed ‘myoCAFs’ and ‘iCAFs’, with the prefixes alluding to a myofibroblast phenotype and regulation of inflammation, respectively.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [49]
The Results section, “Landscape of expression heterogeneity in head and neck cancer” (page not provided), describes reproducible fibroblast subsets, including contractile myofibroblasts and CAFs expressing ligands and extracellular-matrix genes. It does not characterize the CAF subsets as an immunomodulating secretome or call them myoCAFs and iCAFs; it calls the two CAF subtypes CAF1 and CAF2. (LLM, conf=0.85)
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“Cells of the microenvironment coming from different patients can easily group together, showing the absence of a major batch effect between samples, while tumor cells form distinct clusters 4 – 9 .”
Background
- Authors
- Puram, S. V., Tirosh, I., Parikh, A. S., Patel, A. P., Yizhak, K., Gillespie, S., Rodman, C., Luo, C. L., Mroz, E. A., Emerick, K. S., Deschler, D. G., Varvares, M. A., Mylvaganam, R., Rozenblatt-Rosen, O., Rocco, J. W., Faquin, W. C., Lin, D. T., Regev, A., & Bernstein, B. E.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Tirosh, Itay
- Lin, Derrick T.
- Regev, Aviv
- Bernstein, Bradley E.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 171
- Issue
- 7
- Pages
- 1611-1624.e24
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5878932
- OpenAlex
- W2771542157
- Cited by
- 2,557
- References
- 55
- Citations by year
- 2026: 306 · 2025: 319 · 2024: 358 · 2023: 342 · 2022: 354 · 2021: 346 · 2020: 277 · 2019: 159 · 2018: 92 · 2017: 1
- FWCI
- 59.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- American Academy of Otolaryngology
- New England Otolaryngology Society
- Human Frontiers Science Program
- NRSA
- Massachusetts Eye and Ear Infirmary
- National Cancer Institute
- NIH
- Broad Institute
- Klarman Cell Observatory
- Starr Foundation
- Ludwig Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- head and neck squamous cell carcinoma, tumor microenvironment, lymph node metastasis, epithelial-mesenchymal transition, tumor stroma, tumor immune cells, single-cell transcriptomics, tumor heterogeneity, hypoxia, tumor grade, metastasis prediction
- MeSH terms
- Carcinoma, Squamous Cell, Cells, Cultured, Head and Neck Neoplasms, Humans, Male, Neoplasm Metastasis, Gene Expression Profiling, Epithelial-Mesenchymal Transition, Single-Cell Analysis, Tumor Microenvironment
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