Researchers have identified a mechanism that could help determine whether a cancer patient will respond to immunotherapy.
Researchers have identified a mechanism that could help determine whether a cancer patient will respond to immunotherapy. Ideally, the immune system identifies tumours as threatening elements and deploys immune cells (T cells) to find and kill them, according to the study published in the journal Cell Reports. However, tumour cells have evolved to employ a protein called PD-L1 to blind T cells from carrying out their functions and evade immune defences.
PD-L1 protects tumour cells by activating a “molecular brake” known as PD-1 to stop T cells. In important therapeutic progress, antibodies developed to block PD-L1/PD-1 have been clinically proven to benefit certain cancer patients. Yet why some patients do not respond to such therapy has remained a mystery.
Now, researchers from the University of California San Diego in the US and the Nanjing Medical School in China have uncovered some clues. They discovered an unexpected twist in a tumour versus T cell battle. Some tumour cells display not only their PD-L1 weapon but also the PD-1 “brake.”
This simultaneous expression leads PD-1 to bind and neutralise PD-L1 on the same tumour cell. Thus, the PD-L1 on these tumour cells can no longer engage the PD-1 brake on T cells. “It’s a very exciting finding. Our study uncovered an unexpected role of PD-1 and another dimension of PD-1 regulation with important therapeutic implications,” said Enfu Hui from UC San Diego.
This study suggests that patients with high levels of PD-1 on tumour cells may not respond well to the blocking antibodies because the PD-1 pathway is self-cancelled. In these patients, mechanisms other than PD-L1/PD-1 are likely employed by the tumours to escape from immune destruction.
Looking to extend the immunotherapy potential of the finding, Hui and his colleagues are now seeking to determine additional mechanisms of “self-cancellation” at the interface of a tumour and immune cells.