B-Cell-Based Immunotherapy: A Promising New Alternative

Abstract

The field of immunotherapy has undergone radical conceptual changes over the last decade. There are various examples of immunotherapy, including the use of monoclonal antibodies, cancer vaccines, tumor-infecting viruses, cytokines, adjuvants, and autologous T cells carrying chimeric antigen receptors (CARs) that can bind cancer-specific antigens known as adoptive immunotherapy. While a lot has been achieved in the field of T-cell immunotherapy, only a fraction of patients (20%) see lasting benefits from this mode of treatment, which is why there is a critical need to turn our attention to other immune cells. B cells have been shown to play both anti- and pro-tumorigenic roles in tumor tissue. In this review, we shed light on the dual nature of B cells in the tumor microenvironment. Furthermore, we discussed the different factors affecting the biology and function of B cells in tumors. In the third section, we described B-cell-based immunotherapies and their clinical applications and challenges. These current studies provide a springboard for carrying out future mechanistic studies to help us unleash the full potential of B cells in immunotherapy.

Keywords: B cell receptor; B cells; Breg; IgG; IgM.

Figure 1

Dual nature of B cells in the cancer tumor microenvironment. Their anti-tumor characteristics can be utilized to empower immunotherapy goals. While behaving as anti-tumorigenic (left panel), B cells can recognize tumor-specific “neoantigens” and can stimulate antibody production, thus killing oncogenic cells. B cells can also have a pro-tumorigenic effect and promote tumor growth. Circulating immune complexes (CICs) and specific types of B cells (e.g., CD19+, CD24+, and CD38+) are the main factors behind this. These Breg cells differentiate due to inflammation and various other factors. They are responsible for immune tolerance and enhance Foxp3 expression in Treg cells. However, in some hepatocellular carcinomas, the expression of PD1/PD-L1 can suppress the anti-tumor activity of Bregs.

Figure 2

Key factors affecting B-cell function and tumor survival. Once a B cell interacts with tumor cells, it can generate different types of responses, including the secretion of antibodies. This can result in apoptosis, phagocytosis, opsonization, or direct killing of the target cancerous cells or tumors.