PD-1 is a pathway that regulates our immune system and prevents it from destroying healthy tissue when fighting infections. It responds to chemical signals in the body and either turns up the immune response by sending out T-cells to fight infection, or lets cells through without attacking them.
“Think of PD-1 as a lock,” says Dr. Kenneth Bloom, Chief Medical Officer at Clarient. “When a key opens PD-1, the pathway is activated, T-cells are held back, and the immune system doesn’t attack healthy tissue.” Without PD-1 activation, T-cells do their duty and fight off intruders.
Cancer cells have figured out how to trick the PD-1 checkpoint into holding back an immune system reaction. They highjack the pathway by expression PD-L1 on the tumor cell surface to suppress the ability of T-cells to kill tumor cells, allowing tumors to grow and spread through the body.
Keytruda, a drug which has been recently approved by the FDA for the treatment of metastatic non-small cell lung cancer in patients whose tumors express PD-L1, works to manipulate PD-1 back in our favor, turning the tables on cancer. This is why having a precise diagnostic test to predict patients’ response to Keytruda is so important.
The way Keytruda works is simple: it blocks the PD-1 pathway. Without their ability to activate PD-1, PD-L1 expression cancer cells can no longer stop the onslaught of T-cells from doing their job. The T cells recognize the cancer cells, and promptly attack them. This is the basis of immunotherapy, one of the most promising areas of anti-cancer medicine today.
The test, produced by Dako, is an immunohistochemical (IHC) assay that measures a patient’s level of PD-L1, a biomarker that directly correlates with PD-1 activation and has been shown to predict a patient’s likelihood of response with Keytruda.
Pathologists will run the PD-L1 test to help doctors prescribe Keytruda to patients who express PD-L1 in their tumors. “By aligning with Clarient, healthcare providers get an expert laboratory to perform the actual test itself, and access to expert pathologists that can provide the appropriate interpretation of that assay,” said Dr. Bloom.
Lung cancer is the leading cause of cancer deaths in the United States, and the second most common cancer in both men and women. The risk of developing lung cancer is highest in smokers, but many people who do not smoke also develop the disease.
This new test is a sign of the times: the cutting edge of medicine is all about precision. “There are so many characterizations of cancers that we test for and classify at Clarient, that this type of precision diagnostics is what we do best,” said Dr Bloom. “In a world where individualized medicine is the new norm, the information we glean from running the PD-L1 assay will be invaluable for physicians looking to include Keytruda as an option for their patients.”