Harnessing B cells for cancer immunotherapy

B cells are one of the two adaptive arms partnering with T cells in immune defense system against infections by virus, bacteria, fungi and parasites [1]. Originated from hematopoietic stem cells in bone marrow, B cells contain multiple subsets including antibody-secreting cells, antigen-presenting cells (APC), innate B effector cells and regulatory B cells [2]. As a heterogeneous population, B cells possess multidirectional immune functions. For instance, B cells can produce antigen-specific antibodies in response to infectious pathogens or sterile self-antigens [3]. B cells can also present pathogen-derived antigens to T cells during infections [4]. B effector cells can further produce a variety of immune-stimulatory cytokines such as IL-1, IL-6, IL-12 [5], Granulocyte-macrophage colonystimulating factor (GM-CSF) [6], augment immune response against infections or promote inflammation in autoimmune diseases [6,7]. In contrast, regulatory B cells secrete immune-suppressive cytokines including IL-10 and transforming growth factor-β (TGF-β) to attenuate proinflammatory immune response [8]. Emerging evidences show that B cells also have anti-tumor function [9,10]. In preclinical animal model, B cells are required for the successful combined antibody-immunotherapy against murine mesotheliomas [11]. In patients with malignancies, B cells are also found to correlate with a significant increase of overall survival, and higher number of B cell infiltrates lead to better prognosis [12]. However, B cells in particular regulatory B cells can also act as immunesuppressive cells and facilitate tumor immune escape [13,14]. The dual functional faces of B cells on tumors are likely due to the different B cell subpopulations, which have distinguished phenotypes and secretomes that either inhibit tumor growth or facilitate malignancy [9].