Figure 2.

Evidence-based contribution of B lymphocytes to progression of pancreatic adenocarcinoma. B cells infiltrate PDAC in response to the release of local chemokines, such as CXCL13, and can contribute to both tumour promotion and tumour suppression through a variety of mechanisms. Tumour derived IL-18 can induce B lymphocytes with a regulatory phenotype that inhibit anti-tumour cytotoxic T cells responses. B-regulatory cells also secrete immune-modulatory cytokines such as IL-35 and IL-10 that induce T-regulatory cells (Tregs), stimulate tumour proliferation, and promote local angiogenesis. In addition, B-regulatory cells can recruit monocytes to tumour site and foster their differentiation into TGF-β and IL-10 producing M2 macrophages, thus further amplifying immune-evasive strategies and impairing cytotoxic responses. On the other hand, tumour-suppressive activity of B-cells in PDAC has not been clearly established but in-vitro studies suggest that it might depend on the production of autoantibodies against tumour associated antigen (TAA), engagement of natural killer cells (NK cells), and antigen dependent cell-mediated cytotoxicity (ADCC). Finally, plasma cells can sustain activation of the tumour stroma through the secretion of proliferative stimuli for cancer-associated fibroblasts (CAFs), such as PDGFB, and the production of enzymes that regulate extracellular matrix stiffness, such as LOXL2. Whether these properties ultimately exert tumour suppressive or tumour promoting effects is currently under investigation.