Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer

By Sidharth V. Puram, I. Tirosh, Anuraag S. Parikh, Anoop P. Patel, K. Yizhak, Shawn M. Gillespie, Christopher Rodman, C. Luo, E. Mroz, K. Emerick and 9 more. Cell, 2017

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SUMMARY 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.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/6dc2dc471c7b927eb46fff14911c4aef2ae1afaf

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Citations in the corpus

Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020, background): “Natural killer (NK) and T cell clusters included CD4 and CD8 conventional and exhausted T cells, regulatory T cells (Treg), and naive-like T cells (Figure 1D), all bearing resemblance to subsets from prior solid tumor scRNA-seq studies (Guo et al., 2018; Puram et al., 2017; Savas et al., 2018; Tiros”
An integrative model of cellular states, plasticity and genetics for glioblastoma (2019, positive): “Malignant cells varied considerably between tumors (Figures 1C and S1D), consistent with prior studies that showed that malignant cells differ between patients to greater extent than non-malignant cells (Puram et al., 2017; Tirosh et al., 2016a; Tirosh et al., 2016b).”
EMT subtype influences epithelial plasticity and mode of cell migration (2018, background): “The P-EMT program may thus confer tumor cells with invasive properties while simultaneously allowing them to retain intercellular cohesions that facilitate collective behavior (Cheung et al., 2013; Lambert et al., 2017; Liu et al., 2014b; Puram et al., 2017; Revenu and Gilmour, 2009; Westcott et al.”
Spatially organized multicellular immune hubs in human colorectal cancer (2021, background): “, plasmacytoid dendritic cell [pDC] program), and/or expressed in continuous gradients within or across clusters; (2) finding of shared biological properties of malignant cells across individuals despite strong individual-specific transcriptional states (Patel et al., 2014; Puram et al., 2017); and ”