New method to stratify lung cancer patients for immunotherapy
Researchers at IGP have developed a new way of predicting which lung cancer patients are more likely to benefit from immunotherapy. The method could eventually be used to stratify patients before choosing a treatment.
One way of treating cancer is a type of immunotherapy where drugs are used to inhibit the ‘brake’ that cancer cells create to avoid being attacked by the body's own immune system. Such drugs are called checkpoint inhibitors and they simply block the interaction between two molecules that would otherwise result in a suppressed immune response. One group of such drugs now used to treat several different cancers is called PD1/PD-L1 inhibitors.
Unfortunately, only a minority of patients have a durable response to PD1/PD-L1 inhibitors. In addition, the treatment effect is difficult to predict. To optimise the benefits of PD1/PD-L1 inhibitors, it is therefore important to know which patients are most likely to respond to treatment.
In the current study, the researchers tested a new way to stratify lung cancer patients. The method involves detecting whether the molecules PD1 and PD-L1 interact with each other directly in the patients' tumour tissue.
“Our method is based on the idea that the cancer cells' brake on the immune response occurs when PD1 molecules bind to PD-L1 molecules. We used the second-generation PLA technology, which can detect interactions between two specific molecules, and were surprised by how well it worked. Even though we used small diagnostic samples, the technique clearly shows if, and where, the PD1 and PD-L1 molecules have bound to each other,” says Carina Strell, who led the study together with Patrick Micke.
When the researchers compared the presence of PD1-PD-L1 interactions in different cancer types, they found fewer interactions in cancer types that often respond poorly to treatment with PD1/PD-L1 inhibitors. In contrast, cancers with high response rate to PD1/PD-L1 inhibitor treatment had higher levels of PD1-PD-L1 interactions.
“In lung cancer patients treated with PD1/PD-L1 inhibitors at Uppsala University Hospital, we saw that patients who showed more PD1-PD-L1 interactions had responded better to treatment and had a longer survival than those who had fewer interactions. This is very exciting,” says Amanda Lindberg, PhD student in the project and first author of the research article.
The detection of PD1-PD-L1 interactions also worked better in predicting the response to treatment with PD1/PD-L1 inhibitors compared to current methods that only detect the presence of PD-L1.
“In this project, we have collaborated with the company Navinci Diagnostics, that has developed the second generation of PLA technology. Our results show that good relationships between academia and biotech companies can lead to clinically relevant success. The method should now be tested in the clinic as an improved diagnostic tool to stratify cancer patients for immunotherapy treatment,” says Patrick Micke.
In the future, the research team hope to develop several potential diagnostic tests based on PLA technology, that can help cancer patients and their doctors in choosing the most effective drugs.
The study has been published in Journal of Thoracic Oncology.