Newly Discovered Process May Lead Cancer Tumors to Neutralize Themselves
The immune system, a collection of responses that the body makes to protect itself against illness and infection, has long been suspected to be capable of helping to fight cancer. Now a new study published this week in the journal Cell Reports has revealed the discovery of a new mechanism that helps the immune system neutralize cancer tumor cells.
“It’s a very exciting finding,” said study co-author University of California San Diego (UC San Diego) Enfu Hui. The work, undertaken in cooperation with the University of Chicago and the Nanjing Medical School in China, could be used to evaluate whether cancer patients will respond effectively to immunotherapy.
A new protein role uncovered
The scientists discovered this new process by re-evaluating the role of the PD-L1 protein, a compound in tumor cells that inhibits the immune system from carrying out its self-protecting tasks. Under normal circumstances, a healthy immune system will identify tumor cells as threatening entities and deploys T cells, also known as immune cells, to locate and destroy them.
Unfortunately, tumor cells make use of the PD-L1 protein to essentially "blind T cells from carrying out their functions." The protein activates a “molecular brake” known as PD-1 that stops T cells dead in their tracks.
Throughout the years, some research has seen the development of antibodies that can stop PD-L1/PD-1, but the therapies have not been effective on all patients. This may soon no longer be the case.
A self-canceling mechanism
Hui and his team have now discovered a more effective block for PD-L1 that is embedded in the tumor cell's own constitution. It turns out that tumors display both a built-in PD-L1 weapon and a built-in PD-1 "brake."
Uncovering this fact led the scientists to deduce that the protein could then be probed to neutralize itself. “Our study uncovered an unexpected role of PD-1 and another dimension of PD-1 regulation with important therapeutic implications,” explained Hui.
The colleagues are now investigating additional potential mechanisms of “self-cancellation" in the tumor versus immune system battle. “We think that our finding is the tip of the iceberg,” said Hui.
“We speculate that self-cancellation is a general mechanism to regulate immune cell function. Understanding these processes more clearly will help develop better immunotherapy strategies and more reliably predict whether a patient will respond or not,” added the researcher.
In related news, biotechnology company Celgene Corporation released a statement the same day as UC San Diego's study revealing that anti-PD-L1 immunotherapy combined with the firm's drug ABRAXANE "significantly reduced the risk of disease worsening or death" in patients with phase 3 breast cancer. "The IMpassion130 results are extremely encouraging for patients with this highly aggressive form of breast cancer for which there are limited options," said Jay Backstrom, M.D., Chief Medical Officer for Celgene.