2024-10-28 マックス・プランク研究所
<関連情報>
- https://www.mpg.de/23642984/1024-vasb-new-imaging-analysis-method-revolutionizes-the-diagnosis-of-head-and-neck-tumors-154090-x
- https://www.cell.com/cell/fulltext/S0092-8674(24)01146-2
マルチパラメーターイメージングにより、頭頸部癌における臨床的に関連性のある癌細胞-間質相互作用の動態が明らかになる Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer
Karolina Punovuori ∙ Fabien Bertillot∙ Yekaterina A. Miroshnikova∙ … ∙ Antti Mäkitie ∙ Johanna Ivaska ∙ Sara A. Wickström
Cell Published:October 28, 2024
DOI:https://doi.org/10.1016/j.cell.2024.09.046
Graphical abstract
Highlights
•Integrative image analysis of cell state and morphology for cancer prognosis
•Combined tumor-stroma profiles generate clinically relevant phenotypic signatures
•Disease outcome of pEMT signature patients is highly sensitive to stromal composition
•pEMT state is required for pro-invasive reprogramming by cancer-associated fibroblasts
Summary
Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution. By combining cell-state markers with morphological features, we identify phenotypic signatures that correlate with clinical features, including metastasis and recurrence. Integration of tumor and stromal signatures reveals that partial epithelial-mesenchymal transition (pEMT) renders disease outcome highly sensitive to stromal composition, generating a strong prognostic and predictive signature. Spatial transcriptomics and subsequent analyses of cancer spheroid dynamics identify the cancer-associated fibroblast-pEMT axis as a nexus for intercompartmental signaling that reprograms pEMT cells into an invasive phenotype. Taken together, we establish a paradigm to identify clinically relevant tumor phenotypes and discover a cell-state-dependent interplay between stromal and epithelial compartments that drives cancer aggression.
