New research reveals that the PD-1 immune cell receptor works best as dimers, contrary to prior beliefs that it functions alone. This finding has significant implications for improving cancer immunotherapies and treating autoimmune diseases by targeting PD-1’s dimerization. The study highlights a promising direction for designing more effective treatments by adjusting PD-1’s ability to control immune responses.
Among the most important checkpoints is a protein called programmed cell death receptor 1 , which is shut down by a relatively new drug class called checkpoint inhibitors to make tumors “visible” again to immune attack. Such drugs are at least somewhat effective in a third of patients with a variety of cancers, say the study authors, but the field is urgently seeking ways to improve their performance and scope.
Study results showed that PD-1 forms a dimer through interactions of its transmembrane segment. Researchers say this finding is in sharp contrast to other immune receptors, which typically form dimers through the segment of the receptor that is outside the cell. “Our study reveals that the PD-1 receptor functions optimally as dimers driven by interactions within the transmembrane domain on the surface of T cells, contrary to the dogma that PD-1 is a monomer,” said study lead investigator and physician-scientist Elliot Philips, MD, PhD, an internal medicine resident at NYU Grossman School of Medicine and Perlmutter Cancer Center. Philips is also an alumnus of the Vilcek Institute of Biomedical Sciences at NYU.