Immune System “Memories” Guide Treatment Decisions for Lung Cancer Patients

It is now possible, for example, to produce stable long-term remissions in some advanced lung-cancer patients by a process called immune checkpoint therapy.

Checkpoint therapies are, however, effective in only one-in-five patients, are very expensive and can induce severe side-effects.

Now a Sydney Health Partners-funded project has developed a novel blood test which can predict a patient’s response to checkpoint therapy before initiating the treatment.

The test is unusual in measuring the set state of the patient’s immune system, rather than the more usual approach of measuring its response to the therapy itself.

Sydney Local Health District University of Sydney immunologist Professor Barbara Fazekas de St Groth has identified a predictive “signature” of immune cells which she has shown is common to lung cancer patients who do not respond positively to checkpoint therapy.

“This is a major breakthrough in the field because no longer will 80% of patients undergo expensive and potentially life-threatening therapy for no clinical benefit,” said Professor Fazekas.

“The differences that our test reveals between the immune compartment of patients who do or do not respond to therapy are profound. It’s a very positive indicator that the test will prove robust when scaled up for wide application in clinical settings.”

While immune checkpoint inhibitor therapy can help the immune system fight cancers, it can also allow the immune system to attack some normal organs in the body.  This can lead to side effects including fatigue, cough, nausea, loss of appetite, skin rash, and itching. Less often they can cause more serious problems in the lungs, intestines, liver, kidneys, hormone-making glands, or other organs.

The blood test for the effectiveness of checkpoint therapy was developed using the University of Sydney’s Ramaciotti Centre CyTOF (cytometry by time of flight) mass cytometer, which can track up to 100 different cellular processes simultaneously and interrogate a thousand cells a second

Professor Fazekas is confident, however, that the same test can be undertaken for lung cancer patients using more commonly available equipment.

“Medicine is all about what works and this approach is easy and isn’t going to take that long,” she said. “There are ways to do the test which are relatively quick and affordable and can be done at scale.”

Professor Fazekas says the discovery of an immune system signature could also be important for research into auto-immune diseases.

“The immune system is adaptive and its current state has been shaped by events in the lifetime of your body,” she said.

“We know that the immune system carries “memories” – traces of what has happened to it in the past – and that in practical terms these traces are predictive of what will happen in the future.”