PD-1/PD-L1 blockade antibodies can fight against cancer by enhancing the function of macrophages

PD-1, a 55 kDa transmembrane protein, is an immune checkpoint receptor expressed by activated T cells, B cells, and myeloid cells. It is important for the induction of immune tolerance. Mice lacking PD-1 exhibit a breakdown of peripheral tolerance and show multiple autoimmune features. Tumor cells often express elevated levels of PD-L1, which is the ligand for PD-1, and this help them to evade the body’s immune attacks. Monoclonal antibodies targeting PD-1/PD-L1 interaction are promise in treating various cancers. These antibodies have already been known to unleash T cells, but how they affect macrophages remains unclear. (Cusabio offers PODXL Monoclonal Antibody.)

Now, researchers from Stanford University School of Medicine, University Hospital Basel, and Yale University School of Medicine have found that those antibodies also prompt immune cells to engulf and devour cancer cells. In a paper published online 17 May 2017 in Nature, the researchers report how they made the discovery, which will expand the use of PD-1/PD-L1 blockade antibodies in cancer treatment.

PD-1/PD-L1 blockade antibodies have become an important immunotherapy. It is well established that these antibodies work by stimulating T cells to fight cancer cells. The new study provides a new mechanism by which these antibodies combat cancer.

Irving Weissman, corresponding author of the paper, and colleagues demonstrated that both mouse and human tumour-associated macrophages express PD-1, and this expression increases over time and is associated with poor macrophage phagocytosis ability. Inhibiting PD-1/PD-L1 interaction enhances macrophage phagocytosis, decreases cancer growth, and improve outcome of experimental mice.

by whbio | 2017-05-20 01:10