A novel role for polymeric immunoglobulin receptor in tumour development: beyond mucosal immunity and into hepatic cancer cell transformation

Chronic inflammation is well known as a significant driver of carcinogenesis in settings of human disease, including liver disease and hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is one of the major causes of HCC due to the oncogenic nature of the virus and the robust inflammatory response in the infected host. Fc receptors (FcR) are specialized receptors found on innate immune cells that recognize and bind to antigen-presenting antibodies, linking the innate and adaptive immune system to respond to circulating foreign bodies, such as viral DNA (1). Increased B-cell activation and antibody production in response to HBV infected liver will lead to increased FcR signalling on circulating innate immune cells and resident-macrophages (Kupffer cells), further enhancing the inflammatory response. Progression to chronic liver inflammation is associated with hyperactivity of B cell immunity, increasing the risk of cancer development due to constant infiltration of immune cells and accumulation of damaged hepatocytes. FcR activation has been previously implicated in carcinogenesis by creating a ‘pro-tumour microenvironment’ within inflammation-mediated damaged tissue through promotion of angiogenesis, epithelial mesenchymal transition (EMT), and increased cell survival (2). Of recent interest is the polymeric immunoglobulin receptor (pIgR), a member of the Fc receptor family, that is widely expressed on epithelial cells and is responsible for transcytosis of IgA/IgM at mucosal surfaces. Few studies have investigated the role of pIgR in cancer, although most have implicated pIgR to be downregulated in cancers of various epithelial origin (3). In this sense, the dysregulation of pIgR in mucosal membranes could limit the first line of defence for immunity against carcinogenic cells, and possibly contribute to malignant transformation