Harnessing a natural killer to fight lung cancer

Making tumours visible to the body’s own natural killer cells could be the key to fighting the deadliest form of lung cancer.

Lung cancer is the leading cause of cancer related deaths world-wide and small cell lung cancer makes up 15 per cent of all new diagnoses. Due its resistance to current treatments and ability to metastasise (spread), only 5 per cent of patients survive.

For over 40 years small cell lung cancer patients were treated with the same ineffective drugs.  New treatments that harness the patient’s immune system to fight their lung cancer have changed the playing field, but so-called “cold tumours” such as small cell lung cancer find ways of becoming invisible to the immune system, limiting the utility of these treatments.

Associate Professor Dan Gough and his team at Hudson Institute of Medical Research are studying how to make these cold tumours visible to the immune system and prevent them spreading to other parts of the body.

He says identifying patients who will respond and enhancing the response in patients who don’t respond to these treatments is the current holy grail.

Harnessing the immune system to help it fight lung cancer

Their research, published in Nature Immunology, highlights the critical role that the innate immune system plays in making tumours visible to the host.

 “The innate immune system is often associated with the body’s response to infection. We show that it is also critical for the body to be able to “see” a tumour as it develops. Without this immune visibility tumours rapidly spread.” A/Prof Gough said.

This research, with collaborators from Monash Health, Cancer Care Manitoba and Peninsula Oncology, is the first to link this innate immune regulatory cascade to the metastatic spread of small cell lung cancer.

Lead researcher, Dr Aleks Guanizo explained: “We identified a cascade in which the protein STAT3 is essential to maintain the expression of an anti-viral sensing protein called STING. If this cascade is lost then tumours become invisible to the host, allowing for metastasis, which is ultimately lethal.” she said.

Two aspects of this research offer hope for potential new treatments for small cell lung cancer:

1. The identification of a specific subset of immune cells called natural killer cells as being essential to survey and limit tumour metastasis.
2. We show that the innate sensor pathway that is essential for tumour immunity is not permanently lost and that it can be re-activated by innate immune activating stimuli including the anti-viral molecule interferon.

“This shows the power of a coordinated response engaging both the innate and adaptive immune systems. Importantly, we identify a possible treatment to turn cold tumours hot which will improve patient outcomes,” said A/Prof Gough.

Innate immunity explained

The innate immune system is your body’s first line of defence against harmful invaders like bacteria and viruses. It responds quickly and doesn’t need prior exposure to recognize threats.

It incorporates physical barriers, such as skin and mucus, cells like macrophages and neutrophils that “eat” germs, and chemical signals like cytokines that trigger inflammation. It also includes specialised proteins that destroy invaders.

Unlike the adaptive immune system, the innate system is non-specific, meaning it targets a broad range of pathogens without “remembering” them. It acts as a rapid response team, buying time for the adaptive immune system to kick in if needed.