The study, published in the journal Nature, shows that far for being just a lump of cells growing out of control, cancer cells participate in active combat with the immune system for their own survival.
The small vesicles called exosomes circulating in the blood and armed with proteins called PD-L1 that cause T cells to tire before they have a chance to reach the tumour and do battle, according to researchers from the University of Pennsylvania in the US.
While primarily focused on metastatic melanoma, the team found that breast and lung cancer also release the PD-L1-carrying exosomes.
The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system. In addition, it also points to a new way to predict which cancer patients will respond to anti-PD1 therapy that disrupts immune suppression to fight tumours and a means of tracking the effectiveness of such therapies.
“Immunotherapies are life-saving for many patients with metastatic melanoma, but about 70 per cent of these patients don’t respond,” said Wei Guo, a professor at University of Pennsylvania. “These treatments are costly and have toxic side effects so it would be very helpful to know which patients are going to respond,” said Guo.
“Identification of a biomarker in the bloodstream could potentially help make early predictions about which patients will respond, and, later on, could offer patients and their doctors a way to monitor how well their treatment is working,” he said.
One of the most successful innovations in cancer therapy has been the use of checkpoint inhibitor drugs, which are designed to block attempts by cancer cells to suppress the immune system to allow tumours to thrive and spread. One of the primary targets for this class of drugs is PD-1, a protein on the surface of T cells.
On tumour cells, they express a counterpart molecule called PD-L1, which interacts with the PD-1 protein on T cells, effectively turning off that cell’s anti-cancer response. Blocking that interaction using checkpoint inhibitors reinvigorates T cells, allowing them to unleash their cancer-killing power on the tumour.
While it was known that cancer cells carried PD-L1 on their surface, researchers found that exosomes from human melanoma cells also carried PD-L1 on their surface. Exosomal PD-L1 can directly bind to and inhibit T cell functions.
Identification of the exosomal PD-L1 secreted by tumour cells provides a major update to the immune checkpoint mechanism, and offers novel insight into tumour immune evasion.