Dissecting intratumor heterogeneity of nodal B cell lymphomas at transcriptional, genetic, and drug response levels

Abstract

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 intratumor heterogeneity. We addressed this issue by studying the heterogeneity of nodal B cell lymphoma 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 of the same patient responded strikingly different 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 lymphoma and highlight the relevance of intratumor heterogeneity for personalized cancer therapy