External cues to drive B cell function towards immunotherapy

Immunotherapy stands out as a powerful and promising therapeutic strategy in the treatment of can-cer, infections, and autoimmune diseases. Adoptive immune therapies are usually centered on modified T cells and their specific expansion towards antigen-specific T cells against cancer and other diseases. How-ever, despite their unmatched features, the potential of B cells in immunotherapy is just beginning to be explored. The main role of B cells in the immune response is to secrete antigen-specific antibodies and provide long-term protection against foreign pathogens. They further function as antigen-presenting cells (APCs) and secrete pro-and anti-inflammatory cytokines and thus exert positive and negative regulatory stimuli on other cells involved in the immune response such as T cells. Therefore, while hyperactivation of B cells can cause autoimmunity, their dysfunctions lead to severe immunodeficiencies. Only suitably activated B cells can play an active role in the treatment of cancers, infections, and autoimmune diseases. As a result, studies have focused on B cell-targeted immunotherapies in recent years. For this, the devel-opment, functions, interactions with the microenvironment, and clinical importance of B cells should be well understood. In this review, we summarize the main events during B cell activation. From the view-point of mechanobiology we discuss the translation of external cues such as surface topology, substrate stiffness, and biochemical signaling into B cell functions. We further dive into current B cell-targeted therapy strategies and their clinical applications. Statement of significance B cells are proving as a promising tool in the field of immunotherapy. B cells exhibit various functions such as antibody production, antigen presentation or secretion of immune-regulatory factors which can be utilized in the fight against oncological or immunological disorders. In this review we discuss the im-portance of external mechanobiological cues such as surface topology, substrate stiffness, and biochemi-cal signaling on B cell function. We further summarize B cell-targeted therapy strategies and their clinical applications, as in the context of anti-tumor responses and autoimmune diseases. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

B cells play a promising role in immunotherapy for cancer and autoimmune diseases. Understanding the development, functions, and interactions with the microenvironment of B cells is crucial for the development of targeted therapies.