B Cells in Breast Cancer Pathology

Abstract

B cells have recently become a focus in breast cancer pathology due to their influence on tumour regression, prognosis, and response to treatment, besides their contribution to antigen presentation, immunoglobulin production, and regulation of adaptive responses. As our understanding of diverse B cell subsets in eliciting both pro- and anti-inflammatory responses in breast cancer patients increases, it has become pertinent to address the molecular and clinical relevance of these immune cell populations within the tumour microenvironment (TME). At the primary tumour site, B cells are either found spatially dispersed or aggregated in so-called tertiary lymphoid structures (TLS). In axillary lymph nodes (LNs), B cell populations, amongst a plethora of activities, undergo germinal centre reactions to ensure humoral immunity. With the recent approval for the addition of immunotherapeutic drugs as a treatment option in the early and metastatic settings for triple-negative breast cancer (TNBC) patients, B cell populations or TLS may resemble valuable biomarkers for immunotherapy responses in certain breast cancer subgroups. New technologies such as spatially defined sequencing techniques, multiplex imaging, and digital technologies have further deciphered the diversity of B cells and the morphological structures in which they appear in the tumour and LNs. Thus, in this review, we comprehensively summarise the current knowledge of B cells in breast cancer. In addition, we provide a user-friendly single-cell RNA-sequencing platform, called “B singLe cEll rna-Seq browSer” (BLESS) platform, with a focus on the B cells in breast cancer patients to interrogate the latest publicly available single-cell RNA-sequencing data collected from diverse breast cancer studies. Finally, we explore their clinical relevance as biomarkers or molecular targets for future interventions.

Identification of an immune classifier for predicting the prognosis and therapeutic response in triple-negative breast cancer

“…Numerous studies have consistently reported that TNBC tumors exhibit a higher infiltration of B-cells than other types of breast cancer. Owing to the recent approval of immunotherapeutic drugs as a treatment option in both early and metastatic settings for TNBC patients, the presence of B-cell populations or tertiary lymphoid structures holds promise as valuable biomarkers for predicting the immunotherapy responses within specific subgroups of breast cancer (Hu et al, 2021a;Li et al, 2023;Toney et al, 2022). Interestingly, we found higher TILs-B and plasma cells in high-risk cluster of TNBC.…”

The expression patterns of different cell types and their interactions in the tumor microenvironment are predictive of breast cancer patient response to neoadjuvant chemotherapy

“…VEGF -mediated upregulation of survivin in Endothelial cells was further implicated in playing central roles in chemoresistance [15]. Additionally, plasmablasts, as precursors of plasma cells, have been associated with better prognosis [19][20], while B-cells have shown both pro- and anti-tumor roles [18][19][20].…”

“…Lymphocyte density and tumor infiltrating lymphocytes have consistently been associated with BC patients achieving pathological complete response (pCR) following NAC and anti-HER2 therapy [7][8][9][10][11]. Additionally, multiple studies have reported the active involvement of TME in therapy resistance [12][13][14], with macrophages, endothelial, and BC stem cells promoting chemoresistance [15][16][17], and B-cells and plasma cells displaying varying roles in NAC response [18][19][20]. However, to our knowledge, no study has yet attempted to quantify the contribution and predictive power of each individual cell type in the TME to chemotherapy response in a systematic and rigorous manner.…”

Dual Functions of T Lymphocytes in Breast Carcinoma: From Immune Protection to Orchestrating Tumor Progression and Metastasis

“…In fact, the crosstalk of T-cells with other innate and acquired immune cells finally determines the outcome. The interaction of B-cells, the humoral arm of the adaptive immune response, and T-cells becomes more pronounced in GCs where T-cells provide help for B-cells to produce more efficient antibodies [211]. In this regard, Gu-Trantien et al showed that in BC tumors, inflammatory milieu including Tfh cells directed B-cell migration and subsequently induced lymphoid structure and GCs formation, and finally led to the generation of long-lived B-cells and plasma cells and the elimination of tumor residues [140].…”