Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling

Hu, Qingxi; Yu, Hong; Pan, Qi; Lu, Guangqing; Mai, Xueying; Xu, Sheng; He, Xiaoying; Guo, Yu; Gao, Linlin; Jing, Zhiyi; Wang, Jiawen; Cai, Tao; Zhang, Yu

doi:10.1038/s41467-021-22300-2

Cited by 97 publications

(53 citation statements)

References 85 publications

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“… 31 A total of 15,982 B cells were detected, accounting for 25.7% of all cells. As a relatively homogeneous population in the TME, following markers reported in other scRNA studies, 32 , 33 B cells could be divided into four main types, namely, plasma B cells ( XBP1 + / MZB1 + ), MALT B cells ( JCHAIN + / IGHA + / IGHM + ), naïve B cells ( MS4A1 + / TCL1A + / IGHD + ), and memory B cells ( MS4A1 + / TCL1A + / CD27 + ) (Fig. 3E).…”

Section: Resultsmentioning

confidence: 95%

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing

et al. 2022

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Nasopharyngeal carcinoma (NPC) has a 10–15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8 + T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3 + dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

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Section: Resultsmentioning

confidence: 95%

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing

et al. 2022

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“…2a ). Combined with reported marker genes 9 , 10 , we identified naïve B cells (clusters 0 and 3), class-switched memory B cells (clusters 2 and 5), CD27 + memory B cells (clusters 1 and 7), CD27 − memory B cells (cluster 6), pre-ASCs (cluster 4), and plasma cells (cluster 8) (Fig. 2b ).…”

Section: Resultsmentioning

confidence: 69%

Single-cell RNA-Seq reveals transcriptional heterogeneity and immune subtypes associated with disease activity in human myasthenia gravis

Yang

Peng

et al. 2021

Cell Discov

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Myasthenia gravis (MG) is a rare autoimmune disease. Although the impact of immune cell disorder in MG has been extensively studied, little is known about the transcriptomes of individual cells. Here, we assessed the transcriptional profiles of 39,243 cells by single-cell sequencing and identified 13 major cell clusters, along with 39 subgroups of cells derived from patients with new-onset myasthenia gravis and healthy controls. We found that B cells, CD4+ T cells, and monocytes exhibited more heterogeneity in MG patients. CD4+ T cells were expanded in MG patients. We reclustered B cells and CD4+ T cells, and predict their essential regulators. Further analyses demonstrated that B cells in MG exhibited higher transcriptional activity towards plasma cell differentiation, CD4+ T cell subsets were unbalanced, and inflammatory pathways of monocytes were highly activated. Notably, we discovered a disease-relevant subgroup, CD180− B cells. Increased CD180− B cells in MG are indicative of a high IgG composition and were associated with disease activity and the anti-AChR antibody. Together, our data further the understanding of the cellular heterogeneity involved in the pathogenesis of MG and provide large cell-type-specific markers for subsequent research.

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“…These genes have been associated with germinal B cells. Notably, one cluster on the 4T1 (cluster 3) displayed a gene signature typical of plasma B cells (high expression of Cd27 , Cd38, Xbp1 ) [ 39 , 40 ] that was not observed in the EMT6 counterpart despite the higher number of subpopulations retrieved. As reported from the scRNA-seq analysis of human nasopharyngeal carcinoma TMEs [ 25 ], a large number of less differentiated B cell subpopulations identified as naive-like cells were found on both the cell line TMEs.…”

Section: Resultsmentioning

confidence: 99%

A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies

et al. 2022

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Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as αPD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.Here, an assessment of the immune landscape in the tumor microenvironment (TME) of two TNBC mouse models has been performed using single-cell RNA sequencing technology. Specifically, immune cells were evaluated in untreated conditions and after treatments with chemotherapy or immunotherapy used as single agents or in combination. A decrease of Treg was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy and an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were enriched in treatments with low efficacy while M1-like macrophages followed an opposite trend. For both models, similar proportions of B cells were detected with an increase of proliferative B cells in treatments involving cisplatin in combination with αPD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC.

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Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling

Cited by 97 publications

References 85 publications

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing

Single-cell RNA-Seq reveals transcriptional heterogeneity and immune subtypes associated with disease activity in human myasthenia gravis

A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies

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