In short-term infections such as a cold or flu, PD-1 helps to regulate an initial strong T cell response, preventing the T cells from over proliferating and attacking the body's own cells after the infection is cleared. But in patients with cancer or chronic infections, blocking PD-1 has proved a highly successful therapeutic strategy that allows the T cells to fight on. "Blocking this pathway reverses T cell exhaustion and improves tumor immunity in humans and antiviral and anti-tumor responses in animal models," Wherry notes. "But a key question has been whether this PD-1 pathway causes exhaustion. Our work shows that it does not."
Aside from helping to better design PD-1 blockade treatments, Wherry's findings have also helped to identify potential biomarkers in the PD-1 signaling pathway. This additional information will help in the next steps of the research, which involve more detailed study of the PD-1 at different points in its pathway and with different viral or tumor loads. "We still don't know the molecular signals downstream of PD-1 in vivo or how PD-1 signals intersect with other immunotherapies," Wherry says. "We are actively addressing these questions."