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bioRxiv · 10.1101/2022.03.04.482793

Four tumor micro-environmental niches explain a continuum of inter-patient variation in the macroscopic cellular composition of breast tumors.

El Marrahi, A.·Lipreri, F.·Alber, D.·Hausser, J.
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Abstract

The tumor microenvironment is a complex, self-organising tissue whose architecture determines prognostic and response to therapy. There is significant variation in the cellular and spatial architecture of the tumor-microenvironment within and across patients. Are there rules that constrain the architecture of the tumor-microenvironment? To find out, we develop a quantitative framework of tumor architecture inspired by ideas from satellite imaging, which we apply on deep single-cell profiling and multiplex imaging data in breast tumors. Data analysis shows that inter-patient variation in the macroscopic cellular composition of tumors is structured as a continuum explained by four tumor niches: cancer, inflammatory, tertiary lymphoid structure and fibrotic/necrotic. These niches have their origin in tumor micro-architecture and are shared across patients and tumor subtypes. Niche prevalence depends strongly on the patient, which constraints and explains inter-patient variation. The present framework will facilitate interpreting inter-patient variation in terms of a tractable number of micro-environmental niches which serve as organizational entities at the meso-scale to bridge the micro- and macro-scales of tumor architecture.

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El Marrahi, A., Lipreri, F., Alber, D., Hausser, J.. 2022-03-05. Four tumor micro-environmental niches explain a continuum of inter-patient variation in the macroscopic cellular composition of breast tumors.. https://doi.org/10.1101/2022.03.04.482793

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