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Dissecting intratumour heterogeneity of nodal B-cell lymphomas at the transcriptional, genetic and drug-response levels

Tobias Roider, Julian Seufert, Alexey Uvarovskii, Felix Frauhammer, Marie Bordas, Nima Abedpour, Marta Stolarczyk, Jan-Philipp Mallm, Sophie A. Herbst, Peter-Martin Bruch, Hyatt Balke-Want, Michael Hundemer, Karsten Rippe, Benjamin Goeppert, Martina Seiffert, Benedikt Brors, Gunhild Mechtersheimer, Thorsten Zenz, Martin Peifer, Björn Chapuy, Matthias Schlesner, Carsten Müller-Tidow, Stefan Fröhling, Wolfgang Huber, Simon Anders, Sascha Dietrich

Tumour heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is known to affect the efficacy of cancer therapy, most personalized treatment approaches do not account for intratumour heterogeneity. We addressed this issue by studying the heterogeneity of nodal B-cell lymphomas by single-cell RNA-sequencing and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subpopulations and compared their drug-response and genomic profiles. Malignant subpopulations from the same patient responded strikingly differently to anti-cancer drugs ex vivo, which recapitulated subpopulation-specific drug sensitivity during in vivo treatment. Infiltrating T cells represented the majority of non-malignant cells, whose gene-expression signatures were similar across all donors, whereas the frequencies of T-cell subsets varied significantly between the donors. Our data provide insights into the heterogeneity of nodal B-cell lymphomas and highlight the relevance of intratumour heterogeneity for personalized cancer therapy.

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Species: human
Number of cells: 35370
Number of downloads: 66
Study size: 609MB
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lymph node