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The emerging roles of B cells in cancer development

Cellular & Molecular Immunology (2024)Cite this article

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B cells arise from the bone marrow and differentiate into various functional subsets in the peripheral lymphoid organs and inflammatory sites. Whereas T cells have been recognized as the dominant immune population in the tumor microenvironment, increasing evidence has shown the involvement of B cells in cancer development [1]. Within tertiary lymphoid structures (TLSs), which consist of aggregates of spatially organized immune cells in tumors, B cells actively interact with other populations and promote immunotherapy responses [1, 2]. However, the cellular heterogeneity, functional diversity, and underlying mechanisms of B-cell subsets across diverse cancer types remain major challenges for dissecting the roles of B cells in tumor development and immunotherapies.

In newly published papers in Science and Cell, two research groups independently established pancancer landscapes of tumor-infiltrating B cells across major human cancer types by integrating single-cell transcriptomes, B-cell-receptor (BCR) repertoires, chromatin accessibility data, and clinical prognostic information [3, 4]. Using public datasets and their generated single-cell RNA sequencing (scRNA-seq) data derived from cancer patients, Ma et al. identified 15 distinct B-cell subsets, whereas Yang et al. discovered a total of 20 fine-grained B-cell subpopulations, both of which showed significant tissue and cancer-type preferences. These two studies successfully characterized major B-cell subsets during different maturation stages, including naïve B cells, pre-germinal center and germinal center (GC)B cells, memory B cells, and plasma cells, on the basis of their hallmark gene expression signatures. Notably, they revealed the molecular phenotypes and functional features of novel B-cell subsets, including stressed B cells and tumor-associated atypical B (TAAB) cells, across cancer types. These novel findings revealed the existence of diverse functional B-cell subsets at the pancancer level and their associations with the clinical prognosis of cancer patients.

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Acknowledgements

Liwei Lu dedicates this work to his mentor Dr Dennis G. Osmond at McGill University for his pioneering work in B cell immunology. This work was supported by the National Natural Science Foundation of China (82071817), the Hong Kong Research Grants Council (17113319, 17103821, 17111222), the RGC Theme-based Research Scheme (TRS) (T12-703/19-R) and the Centre for Oncology and Immunology under the Health@InnoHK Initiative funded by the Innovation and Technology Commission, The Government of Hong Kong SAR, China. The figure was created with BioRender.com with the permission of the publication license.

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Authors and Affiliations

  1. Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China

    Fan Xiao & Liwei Lu

  2. Department of Rheumatology and Immunology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

    Dongmei Zhou

  3. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

    Meng Cao

  4. Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, 410011, Hunan, China

    Haijing Wu

  5. Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China

    Chunxing Zheng & Liwei Lu

  6. Department of Laboratory Medicine, Institute of Medical Immunology of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang, China

    Ke Rui

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  1. Fan Xiao
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Correspondence to Ke Rui or Liwei Lu.

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The authors declare no competing interests. Liwei Lu is editorial board member of Cellular & Molecular Immunology, but he has not been involved in the peer review or the decision-making of the article.

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Xiao, F., Zhou, D., Cao, M. et al. The emerging roles of B cells in cancer development. Cell Mol Immunol (2024). https://doi.org/10.1038/s41423-024-01211-4

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