TY - JOUR
T1 - Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer
AU - Puram, Sidharth V.
AU - Tirosh, Itay
AU - Parikh, Anuraag S.
AU - Patel, Anoop P.
AU - Yizhak, Keren
AU - Gillespie, Shawn
AU - Rodman, Christopher
AU - Luo, Christina L.
AU - Mroz, Edmund A.
AU - Emerick, Kevin S.
AU - Deschler, Daniel G.
AU - Varvares, Mark A.
AU - Mylvaganam, Ravi
AU - Rozenblatt-Rosen, Orit
AU - Rocco, James W.
AU - Faquin, William C.
AU - Lin, Derrick T.
AU - Regev, Aviv
AU - Bernstein, Bradley E.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12/14
Y1 - 2017/12/14
N2 - 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. Single-cell transcriptomic analysis in patients with head and neck squamous cell carcinoma highlights the heterogeneous composition of malignant and non-malignant cells in the tumor microenvironment and associates a partial EMT program with metastasis.
AB - 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. Single-cell transcriptomic analysis in patients with head and neck squamous cell carcinoma highlights the heterogeneous composition of malignant and non-malignant cells in the tumor microenvironment and associates a partial EMT program with metastasis.
KW - epithelial-to-mesenchymal transition
KW - head and neck squamous cell carcinoma
KW - intra-tumoral heterogeneity
KW - metastasis
KW - scRNA-seq
KW - single-cell RNA sequencing
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85035813065&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.10.044
DO - 10.1016/j.cell.2017.10.044
M3 - Article
C2 - 29198524
AN - SCOPUS:85035813065
SN - 0092-8674
VL - 171
SP - 1611-1624.e24
JO - Cell
JF - Cell
IS - 7
ER -