New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms

Abstract

Currently, tumor-infiltrating B lymphocytes have been recognized as a new hallmark of breast cancer (BC). The function seems to be controversial, either with positive, negative, or no significance in BC's prediction and prognosis. Moreover, B-cell infiltrates regulate tumor process through productions of antibodies and interleukin-10. The interactions with other lymphocytes and programmed death-1/PD-1 ligand axis are also documented. The regulatory mechanisms will eventually be incorporated into diagnostic and therapeutic algorithms, thus give guide to clinical treatment. In this review, we give new insights into clinical impacts and regulatory mechanisms of tumor-infiltrating B cells, which heralds a new era in immuno-oncology in BC treatment.

Keywords: breast cancer; checkpoint molecules; prognosis; regulatory mechanism; tumor-infiltrating B lymphocytes.

Figure 1

The regulatory mechanisms of tumor-infiltrating B cells (TIL-B) in breast cancer. (A) For tumor cells, antigens including β-actin and ganglioside GD3, which are derived from cancer cells, can be recognized by TIL-B. TIL-B can also kill tumor cells directly. Moreover, TIL-B can kill cancer cells in CXCR4/CXCL12 pathways by cell-to-cell contact or through Fas/FasL pathways. (B) For other tumor-infiltrating lymphocytes, regulatory functions on regulatory T cells may be engendered through secretion of IL-10 and transforming growth factor (TGF)-β as well as overexpression of PD-1-ligand (PD-L1). As for T-cell response, IgG secretion can facilitate DC-induced T-cell response or inhibit cytotoxic T cells response in the form of IgG-TGF-β complex. T cell inhibition by PD-L1 expression is also involved in the process.