Sometimes our immune systems can destroy cancer. Now more light has been shed on how this happens with the discovery of tiny clumps of immune tissue that form within tumours.
The structures, dubbed immune outposts, seem to improve people’s chances of surviving cancer – and may be turned into a new treatment if they can be encouraged to form artificially.
We have long known that the immune system responds to cancer. Some existing medicines work by boosting this response, but they only lead to a cure in a minority of people.
Haydn Kissick at Emory University School of Medicine in Atlanta, Georgia, and his colleagues looked at tumours removed from about 150 people with cancers of the kidney, bladder or prostate. The proportion of T-cells – the immune cells that fight tumours – within the growths ranged from 0.002 per cent to over 20 per cent of the total number of cells.
The T-cells weren’t randomly distributed within the tumour, but were clustered in the outposts, which were about a tenth of a millimetre across and sited near tiny blood vessels going into the tumours.
As well as the fully developed T-cells, the outposts contained immature T-cells called stem-like cells, which can multiply to produce a constant supply of new immune cells. “They keep pumping out the soldiers,” says Kissick. “You need these things because T-cells are continually dying.”
The outposts also contained a second kind of immune cell that picks up and displays cancer molecules on its surface, highlighting them to T-cells as something that needs to be attacked. “These [outposts] are acting like a lymph node but at the site where the fight is taking place,” says Kissick. “It’s like a ground zero.”
Lymph nodes, small, bean-shaped nodules in places such as the neck and armpits, are where immune cells learn to fight anything harmful such as bacteria – or cancer cells – by recognising molecules on their surface.
“We knew there were [T-cells] in tumours, but this shows where the stem-like cells live,” says Nicholas Restifo of US biotech firm Lyell Immunopharma. “All stem cells have niches where they are kept safe and sound. We had never pinned them anatomically.”
The outposts hadn’t managed to stop the cancers from growing – some were up to 10 centimetres across. But after people had their primary tumour removed, those who had more outposts were less likely to have secondary tumours emerge elsewhere in their body.
This may have been because the T-cells had “learned” to recognise the cancer while in the outposts, says Kissick. “If you have these in your tumour, you seem to control the disease.”
The team is now investigating if some tumours produce chemicals that cause the outposts to break down. “If we can neutralise that, they can pop back up.”
Previously, another kind of immune tissue, known as tertiary lymphoid structures, has been associated with cancer, but this is usually found around the outside of tumours and contains mainly B-cells, which produce antibodies but cannot kill tumour cells.
Other research groups have been trying to make scaffolds out of algae that could be seeded with immune cells and implanted next to or inside a tumour.
“Once you understand that these structures are important for survival, we might be able to manipulate them or encourage their growth,” says Restifo.
Journal reference: Nature, DOI: 10.1038/s41586-019-1836-5