Tumor-Infiltrating B Cell Dynamics in Cancer Immunology

Tumour-infiltrating B cells are emerging as pivotal modulators of cancer immunity. While T cells have traditionally dominated the field, B cells within the tumour microenvironment contribute to antitumour responses through antigen presentation, antibody production and cytokine secretion. These cells frequently organise into tertiary lymphoid structures, undergo local clonal expansion, somatic hypermutation and class-switch recombination to generate high-affinity antibodies. Depending on their phenotype and context, B cells may either promote tumour eradication by recruiting effector cells and producing tumour-specific immunoglobulins or support tumour growth through regulatory subsets and pro-angiogenic factors. Advances in single-cell sequencing, spatial transcriptomics and integrated receptor profiling have illuminated the diverse states and trajectories of intratumoural B cell subsets across multiple cancer types. A deeper understanding of these dynamics offers promising avenues to harness B cells in immunotherapeutic strategies, from optimising antibody discovery to modulating the tumour milieu for improved patient outcomes.

Research from Nature Portfolio

Recent studies have begun to reveal the breadth of B cell functions within solid tumours. In breast cancer, integrative analysis of B cell receptor repertoires alongside tumour genomics and transcriptomics demonstrates that B cell clones coevolve with tumour mutational landscapes, and that highly central B cell antigen receptors can be tracked across metastatic sites, offering routes to prioritise antibodies for therapeutic development. In melanoma, profiling of tumour-resident versus circulating B cells uncovers local clonal expansion, somatic hypermutation, class-switch recombination and an unexpected autoimmune-like polyreactivity in intratumoural antibodies, pointing to both protective and dysregulated humoral responses. Work in ovarian carcinoma highlights a dominant polyclonal IgA response that binds polymeric IgA receptors on malignant cells, driving myeloid cell–mediated cytotoxicity, modulating tumour intracellular signalling and enhancing cytolytic T cell killing, thus orchestrating a coordinated antitumour network.

Tumor-Infiltrating B Cell Dynamics in Cancer Immunology publication trend

The graph below shows the total number of articles in tumor-infiltrating b cell dynamics in cancer immunology across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour microenvironment: The complex milieu of cancer cells, stromal elements and immune populations in which tumours develop and progress.

Tumour-infiltrating B cells (TIL-B cells): B lymphocytes present within the tumour microenvironment that engage in antigen presentation, antibody production and modulation of antitumour immunity.

B cell receptor (BCR) repertoire: The diversity of antigen-specific receptors expressed by B cells, reflecting clonal selection, somatic hypermutation and class switching.

Germinal centre-dependent response: A pathway in secondary lymphoid structures where B cells undergo somatic hypermutation and affinity maturation under the guidance of follicular helper T cells.

Somatic hypermutation: An enzymatic process in germinal centres that introduces point mutations into immunoglobulin variable regions to increase antibody affinity.

Class switch recombination: A DNA recombination event by which B cells change antibody isotype (for example from IgM to IgG or IgA) without altering antigen specificity.

Tertiary lymphoid structures: Ectopic, lymph node-like aggregates that form within tumours and support local adaptive immune responses.

References

1. Predictability of B cell clonal persistence and immunosurveillance in breast cancer. Nature Immunology (2024).
2. Germinal center-dependent and -independent immune responses of tumor-infiltrating B cells in human cancers. Cellular & Molecular Immunology (2023).
3. B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma. Nature Communications (2023).
4. IgA transcytosis and antigen recognition govern ovarian cancer immunity. Nature (2021).
5. Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma. OncoImmunology (2019).