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Solving the Mystery of PD-1 Inhibitors

RESEARCHERS in Canada have solved the mystery of how programmed cell death protein 1 (PD-1) inhibitors work on the immune system’s natural killer (NK) cells. Trogocytosis has been discovered to play a key role between the immune system and blood cancer cells. This ‘kiss’ between cells has revealed how checkpoint inhibitor cancer drugs work on the immune system’s NK cells. 

Trogocytosis is a process where immune cells, for example NK cells, connect with another cell type and steal part of their membrane. Researchers at the University of Ottawa and The Ottawa Hospital, Ontario, Canada, discovered that this process also involves a protein called PD-1, which gives an immune cell the ‘kiss of sleep’, and prohibits its cancer-fighting abilities.  

Michele Ardolino, Senior Scientist at The Ottawa Hospital and Assistant Professor at the University of Ottawa, commented on his team’s significant research: A missing piece of the puzzle is how NK cells produce PD-1, which was surprisingly hard to address. Now we understand why: NK cells do not make their own PD-1, but they steal it from cancer cells! We don’t know exactly why NK cells steal membranes from cancer cells, but it seems clear that tumours hijack the process to put NK cells to sleep and evade the immune system.” 

PD-1 inhibitors are routinely used to revitalise the immune system and help it to fight off cancer cells. These PD-1 inhibitors were originally developed in order to wake up the T cells of the immune system. For patients with certain types of skin, blood, or lung cancer, their use has significantly improved prognosis. 

The team, which is made up of a large number of staff, trainees, and postdoctoral fellows across both institutions, believe that understanding this process could lead to the future development of new cancer immunotherapy drugs. With this important new breakthrough, the Ottawa team may have paved the way for to improve outcomes for patients globally.