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.

肿瘤异质性包括恶性细胞及其微环境。虽然已知个体患者之间的异质性会影响癌症治疗的疗效，但大多数个性化治疗方法并未考虑肿瘤内的异质性。我们通过单细胞 RNA 测序和转录组信息流式细胞术研究淋巴结 B 细胞淋巴瘤的异质性来解决这个问题。我们鉴定了转录上不同的恶性亚群，并比较了它们的药物反应和基因组谱。来自同一患者的恶性亚群对体外抗癌药物的反应明显不同，这概括了体内治疗期间亚群特异性药物敏感性。浸润性 T 细胞代表了大多数非恶性细胞，其基因表达特征在所有供体中相似，而 T 细胞亚群的频率在供体之间显着不同。我们的数据提供了对淋巴结 B 细胞淋巴瘤异质性的见解，并强调了肿瘤内异质性与个性化癌症治疗的相关性。