The human immune system has the power to fight off a vast array of viruses, infections and other pathogens. Yet when cancer strikes, that often isn’t enough. In some forms of the disease, tumor cells hide in plain sight, evading a patient’s T cells — parts of the immune system key to destroying pathogens. If a cancer evades them for long enough, the immune cells enter a state called “T cell exhaustion,” where those powerful defenders call off their attack, and linger in the background.
John Wherry, an immunologist at the University of Pennsylvania, thinks a promising type of immunotherapy (a family of treatments that manipulate the body’s own immune system to fight disease) could reverse this exhaustion, helping patients with melanoma and other similar cancers. In those diseases, tumors hide from the body’s T cells by attaching a molecule called PD-L1 onto their surface. The T cells sniff out this molecule to distinguish friend from foe: If they encounter a cell with PD-L1 on its surface, they ignore it and move on without a fight. Cells without PD-L1 aren’t so lucky — the T cells immediately attack and destroy them.
T cells detect these friend-or-foe molecules via a lock-and-key receptor called PD-1. Blocking PD-1 can spur the T cells to attack invaders with renewed vigor. Treatments based on this mechanism have turned cancers that were a death sentence into curable diseases — but it’s far from a perfect system and many questions remain.
- Interview with immunologist John Wherry here
John Wherry, an immunologist at the University of Pennsylvania, thinks a promising type of immunotherapy (a family of treatments that manipulate the body’s own immune system to fight disease) could reverse this exhaustion, helping patients with melanoma and other similar cancers. In those diseases, tumors hide from the body’s T cells by attaching a molecule called PD-L1 onto their surface. The T cells sniff out this molecule to distinguish friend from foe: If they encounter a cell with PD-L1 on its surface, they ignore it and move on without a fight. Cells without PD-L1 aren’t so lucky — the T cells immediately attack and destroy them.
T cells detect these friend-or-foe molecules via a lock-and-key receptor called PD-1. Blocking PD-1 can spur the T cells to attack invaders with renewed vigor. Treatments based on this mechanism have turned cancers that were a death sentence into curable diseases — but it’s far from a perfect system and many questions remain.
- Interview with immunologist John Wherry here
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