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| Item Type: | Preprint |
|---|---|
| Title: | High-resolution molecular atlas of a lung tumor in 3D |
| Creators Name: | Pentimalli, T.M., Schallenberg, Simon, León-Periñán, D., Legnini, I., Theurillat, I., Thomas, G., Boltengagen, A., Fritzsche, S., Nimo, J., Ruff, L., Dernbach, G., Jurmeister, P., Murphy, S., Gregory, M., Liang, Y., Cordenonsi, M., Piccolo, S., Coscia, F., Woehler, A., Karaiskos, N., Klauschen, F. and Rajewsky, N. |
| Abstract: | Cells live and interact in three-dimensional (3D) cellular neighborhoods. However, histology and spatial omics methods mostly focus on 2D tissue sections. Here we present a 3D spatial atlas of a routine clinical sample, an aggressive human lung carcinoma, by combining in situ quantification of 960 cancer-related genes across ~340,000 cells with measurements of tissue-mechanical components. 3D cellular neighborhoods subdivided the tumor microenvironment into tumor, stromal, and immune multicellular niches. Interestingly, pseudotime analysis suggested that pro-invasive epithelial-to-mesenchymal transition (EMT), detected in stroma-infiltrating tumor cells, already occurred in one region at the tumor surface. There, myofibroblasts and macrophages specifically co-localized with pre-invasive tumor cells and their multicellular molecular signature identified patients with shorter survival. Moreover, cytotoxic T-cells did not infiltrate this niche but colocalized with inhibitory dendritic and regulatory T cells. Importantly, systematic scoring of cell-cell interactions in 3D neighborhoods highlighted niche-specific signaling networks accompanying tumor invasion and immune escape. Compared to 2D, 3D neighborhoods improved the characterization of immune niches by identifying dendritic niches, capturing the 3D extension of T-cell niches and boosting the quantification of niche-specific cell-cell interactions, including druggable immune checkpoints. We believe that 3D communication analyses can improve the design of clinical studies investigating personalized, combination immuno-oncology therapies. |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2023.05.10.539644 |
| Date: | 10 May 2023 |
| Official Publication: | https://doi.org/10.1101/2023.05.10.539644 |
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