<p id="P1">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.
</p>