B cells and cancer: To B or not to B?

Abstract

Whereas T cells have been considered the major immune cells of the tumor microenvironment able to induce tumor regression and control cancer clinical outcome, a burst of recent publications pointed to the fact that B cells may also play a prominent role. Activated in germinal centers of tertiary lymphoid structures, B cells can directly present tumor-associated antigens to T cells or produce antibodies that increase antigen presentation to T cells or kill tumor cells, resulting in a beneficial clinical impact. Immune complexes can also increase inflammation, angiogenesis, and immunosuppression via macrophage and complement activation, resulting in deleterious impact.

Figure 1.

Impact of B cells and TLSs on prognosis and response to ICIs. Analysis of 15 different tumor types. The surface of the spot is proportional to the number of patients for each cancer, with a favorable impact (green), mostly favorable impact (light green), unfavorable impact (red), or no impact (white) on PFS or OS and therapeutic response to ICIs.

Figure 2.

Mechanisms of action of B cells in cancer. In GCs of TLSs, B cells are selected by antigen presented by FDC-associated immune complexes. They are activated with the help of T follicular helper (Tfh) cells, proliferate, and differentiate into memory B cells and plasma cells. B cells present antigens to CD4 and CD8 T cells. Plasma cells produce IgG antibodies, which may increase antigen presentation to T cells after uptake of immune complexes by DCs and kill or engulf tumor cells via ADCC and ADCP, respectively (right). B cells can also transfer antigen directly to DCs or via complement receptor 2 to FDCs in the form of opsonized immune complexes. Memory B cells and antibodies circulate in the blood, where they help control potential metastatic cells (right). In contrast, binding of immune complexes to macrophages results in their activation and the production of proinflammatory mediators that exert protumor activities. Tumor cell–bound antibodies can also activate complement, which fuels inflammation and activates endothelial cells, promoting tumor growth and spread (left). B reg cells may also inhibit immune responses via the production of IL-10.