Polymeric immunoglobulin receptor (pIgR) in cancer progression: a critical role and potential therapeutic target

Polymeric immunoglobulin receptor (pIgR) is a crucial receptor that primarily mediates the transcytosis of immunoglobulins A and M across epithelial cells, emerging as an essential participant in modulating both mucosal immunity and innate immunity. Recently, pIgR dysregulation in cancer has garnered widespread attention. It exhibits distinct mechanisms and effects across various cancer types with significant clinical value as a biomarker for malignant tumor diagnosis and prognosis evaluation. Recent therapeutic advances have revealed promising strategies, including dimeric IgA-based approaches targeting intracellular oncogenic drivers through pIgR-mediated transcytosis, small molecule modulators such as bufalin, and targeting EV-pIgR with neutralizing antibodies. Integrating these approaches with conventional therapies presents opportunities for enhanced treatment efficacy. Specifically, blocking EV-pIgR with neutralizing antibodies, when integrated with conventional hepatocellular carcinoma therapies such as sorafenib or other therapeutic agents, or a dIgA-targeting approach combined with immune checkpoint inhibitors, may enhance treatment efficacy. This review also addresses current challenges and future directions in pIgR-targeted cancer therapy, emphasizing the need for a deeper understanding of pIgR's regulatory mechanisms. These insights reveal that pIgR is an emerging therapeutic target with significant potential for the development of novel cancer treatment strategies.