B cells, plasma cells and antibody repertoires in the tumour microenvironment

Abstract

Recent data show that B cells and plasma cells located in tumours or in tumour-draining lymph nodes can have important roles in shaping antitumour immune responses. In tumour-associated tertiary lymphoid structures, T cells and B cells interact and undergo cooperative selection, specialization and clonal expansion. Importantly, B cells can present cognate tumour-derived antigens to T cells, with the functional consequences of such interactions being shaped by the B cell phenotype. Furthermore, the isotype and specificity of the antibodies produced by plasma cells can drive distinct immune responses. Here we summarize our current knowledge of the roles of B cells and antibodies in the tumour microenvironment. Moreover, we discuss the potential of using immunoglobulin repertoires as a source of tumour-specific receptors for immunotherapy or as biomarkers to predict the efficacy of immunotherapeutic interventions.

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Fig. 1: Antitumour roles of tumour-infiltrating B cells and intratumourally produced antibodies.
Fig. 2: Protumour roles of tumour-infiltrating B cells and intratumourally produced antibodies.
Fig. 3: Potential advantages of IgG1-biased over IgG3-biased humoral response.

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Acknowledgements

Funding

The work was supported by grants from the Ministry of Education and Science of the Russian Federation (14.W03.31.0005) and Russian Science Foundation (19-14-00317, in part of antibody repertoire analysis methods).

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All of the authors contributed to researching data for the article, the discussion of content and the writing of the article. D.M.C. and G.V.S. reviewed and edited the manuscript before submission.

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Correspondence to Dmitriy M. Chudakov.

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Supplementary information

Glossary

The Cancer Genome Atlas (TCGA) database

The most comprehensive cancer genomics database; it contains multiple types of genomic data with histological information and clinical records for more than 11,000 patients and 33 cancer types.

Cryptic peptide antigens

Antigens that originate from translation of sequences outside annotated open reading frames. They may derive from non-annotated open reading frames, non-coding genomic regions, alternative start codons, frameshift mutations, alternative splicing or ribosomal frameshifting. Protein splicing and post-translational modifications can also be classified as cryptic peptide antigens.

Thomsen–Friedenreich antigen

A tumour-associated carbohydrate antigen highly expressed by approximately 90% of human carcinomas. It is believed to facilitate tumour growth by allowing increased interaction of the tumour cells with carbohydrate-binding lectins.

Immune complexes

Antigen–antibody complexes, may include multiple antigen and antibody molecules, as well as complement proteins. They may modulate activity of myeloid cells, triggering chronic inflammation and tissue remodelling processes, and facilitating formation of myeloid-derived suppressor cells.

Myeloid-derived suppressor cell

An immunosuppressive myeloid cell that develops under chronic inflammatory conditions. These cells can be subdivided into monocytic and polymorphonuclear myeloid-derived suppressor cells.

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Sharonov, G.V., Serebrovskaya, E.O., Yuzhakova, D.V. et al. B cells, plasma cells and antibody repertoires in the tumour microenvironment. Nat Rev Immunol 20, 294–307 (2020). https://doi.org/10.1038/s41577-019-0257-x

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