A single-cell atlas of diffuse large B cell lymphoma

• Published in: Cell reports (Cambridge) 2022-04, Vol.39 (3), p.110713-110713, Article 110713
• Main Authors: Ye, Xiaofei, Wang, Lei, Nie, Man, Wang, Yuyao, Dong, Shichen, Ren, Weicheng, Li, Guibo, Li, Zhi-Ming, Wu, Kui, Pan-Hammarström, Qiang
• Format: Article
• Language: English
• Subjects: diffuse large B cell lymphoma; hepatitis B virus (HBV); Hepatitis B, Chronic; Humans; immunotherapy; Lymphoma, Large B-Cell, Diffuse - metabolism; Medicin och hälsovetenskap; relapse; scRNA-seq; single-cell RNA sequencing; Transcriptome; tumor heterogeneity; tumor microenvironment; Tumor Microenvironment - genetics; Whole Exome Sequencing
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110713

Diffuse large B cell lymphoma (DLBCL) is one of the most common yet aggressive types of B cell lymphoma and remains incurable in 40% of patients. Herein, we profile the transcriptomes of 94,324 cells from 17 DLBCLs and 3 control samples using single-cell RNA sequencing. Altogether, 73 gene expression programs are identified in malignant cells, demonstrating high intra- and intertumor heterogeneity. Furthermore, 2,754 pairs of suggestive cell-cell interactions are predicted, indicating a complex and highly dynamic tumor microenvironment. Especially for B cell lymphomas, a strong costimulatory CD70-CD27 interaction is predicted between malignant and T cells. Furthermore, coinhibitory signals mediated by TIM3 or TIGIT seem to be the main driving force for T cell exhaustion. Finally, we find that chronic hepatitis B virus infection may have a significant impact on tumor cell survival and immune evasion in DLBCL. Our results provide insights into B cell lymphomagenesis and may facilitate the design of targeted immunotherapy strategies. [Display omitted] •High intra- and intertumor heterogeneity in DLBCL is observed by single-cell RNA-seq•TME cells may promote DLBCL activation/survival by CD40- fand BAFF-mediated signals•Coinhibitory signals through TIM3 and TIGIT may drive T cell exhaustion in DLBCL•HBV infection likely contributes to malignant cell survival/immune evasion in DLBCL Using single-cell RNA sequencing, Ye et al. demonstrate that genetic diversity within tumors, potential interactions between malignant and tumor-infiltrating cells, and viral infections may all contribute to the marked disease heterogeneity in DLBCL.