Genetic discovery to improve lung cancer immunotherapy

A research team led by Edith Cowan University (ECU) has found a way to make lung cancer treatment safer and more effective, with their results published in the European Journal of Cancer.

Immunotherapy has emerged as a major weapon in the battle against non-small cell lung cancer, which makes up 80–85% of all lung cancer diagnoses. Unfortunately, immunotherapy can also result in severe side effects for patients: at least 74% of those treated will experience immune-related adverse reactions and up to 21% will develop grade three or four toxicity, which can lead to lifelong complications affecting the skin, gut, liver or endocrine system.

These adverse reactions can result in cancer treatment having to be discontinued, which risks allowing the disease to progress further. But somewhat contradictorily, people who experience these immunotherapy side effects tend to have more positive results with their cancer progression than those who don’t.

“Immunotherapies unleash the immune system to recognise and kill cancer cells,” said study supervisor Associate Professor Elin Gray, from ECU’s Centre for Precision Health.

“But they can also unleash the immune cells to attack the body, causing toxicities.

“Our research shows for the first time that certain genetic features predispose cancer patients to develop side effects or toxicities to anticancer therapy.

“Knowing this will allow doctors to improve the treatment given to patients.”

Key to the research are human leukocyte antigens (HLAs), which are markers found in most cells in the body. The immune system uses HLAs to determine which cells do and don’t belong in your body and are part of the alarm system which detects viruses, infections and cancer.

The research team examined the HLAs of 179 non-small cell lung cancer patients and found a strong link between the genetic make-up of the HLAs and whether the person was likely to develop side effects from immunotherapy. Study lead Dr Afaf Abed said this discovery would benefit all non-small cell lung cancer patients, regardless of whether they were genetically predisposed to adverse reactions to immunotherapy or not.

“If someone is found to not be at risk of side effects, doctors can ramp up the treatment and be more aggressive in fighting the disease,” she said.

“If they are found to be at a higher risk, doctors can take it easier with the treatment, monitor it and intervene before patients develop grade 3 or 4 toxicity.

“Either way, biomarkers that predict the risk of these immune-mediated adverse events among patients may reduce the risks associated with these treatments.”

Image caption: Dr Afaf Abed.

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