Smokers' bodies react differently to lung cancer treatment than non-smokers', scientists have found, which may explain why one in five patients don't respond to immunotherapy.
Researchers believe understanding the differences in lung cancer evolution between smokers and non-smokers could be the key to unlocking new tailored treatments for the deadly disease.
The research team observed a subset of T cells, called TRM, were found to be highly enriched in smokers' lungs, forcing any arising tumours to evolve and evade immunotherapy.
"In these patients, the TRM apply pressure on the tumour to evade the body's immune response," said Professor Daniel Gray of The Walter and Eliza Hall Institute of Medical Research.
"Immunotherapy is less effective against tumours that acquire this property."
Lead researcher Marie-Liesse Asselin-Labat said differences in the immune reactions between smokers and non-smokers may explain why only 20 per cent of patients with lung cancer responded to immunotherapy.
"It shows that we need to take a different approach to treating smoker and non-smoker patients with lung cancer," Associate Professor Asselin-Labat said.
"In smokers, we need to make the tumours visible to the immune system for immunotherapy to be effective, whereas in non-smoker patients we need to activate a dormant immune system to enable it to fight the tumour."
Of the 13,000 Australians diagnosed with lung cancer every year, ten per cent of men and 35 per cent of women have no history of smoking.
Researchers hope to investigate ways of increasing the visibility of the tumour cells to the immune system in lung cancer patients who have been smokers.
"We are using genomic screening to look for epigenetic silencing that might occur so we can then focus on those targets," Assoc Prof Asselin-Labat said.
It would be the first step in developing precision, tailored therapies for patients depending on their smoking history.
Researcher Clare Weeden said understanding the differences in tumour evolution was vital to improving treatment.
"Our work shows the importance of the environment a tumour develops in.
"If we can understand the nature of the pre-existing tissue, we can better work out how tumours evolve over time and develop precision therapy for individuals based on their smoking history," she said.
The research was published in the journal Cancer Cell.
