Is this secret to beating cancer? Scientists could turn off ‘don’t eat me’ signal in disease cells – allowing the immune system to attack them
- Cancer cells give off a ‘don’t eat me’ signal to evade the immune system
- Stanford researchers have found out what it is: a protein called CD24
- By blocking CD24, they were able to better attack the cancer in mice
A major ‘don’t eat me’ signal which cancer cells appear to use to stop the immune system from attacking them has been discovered by US researchers.
Normally, immune cells detect cancer cells and engulf them, but researchers have previously discovered proteins on the surface of cells that can tell them not to do this.
This is useful to ward off attacks on normal, healthy cells, but scientists have found that cancer cells are using these signals to hide.
Researchers at the Stanford University School of Medicine have now discovered a new protein, called CD24, that acts as a potent ‘don’t eat me’ signal ‘capable of directly protecting cancer cells from attack’.
They believe the discovery holds ‘particular promise’ for sufferers of hard-to-treat ovarian and breast cancers, which affect thousands of women each year.
The researchers hope that most cancers will be able to be made vulnerable to attack when one or more of the signals are blocked
When the researchers blocked the CD24 signal in mice implanted with human cancers, they found that this allowed the immune cells, called macrophages, to attack the cancer cells.
This led to a reduction in tumor growth and increase in survival time in the mice.
Researchers from the university have previously shown that the proteins PD-L1, CD47 and the beta-2-microglobulin subunit of the major histocompatibility class 1 complex are all used by cancer cells to protect themselves from immune cells.
Antibodies that block CD47 are in clinical trials, while treatments that target PD-L1 or the PD-L1 receptor are being used in clinics.
A paper describing the research is published in Nature.
Senior author Irving Weissman, professor of pathology and of developmental biology and director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, said: ‘Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative ‘don’t eat me’ signals.’
Lead author Amira Barkal, an MD-PhD student, added: ‘You know that if cancers are growing in the presence of macrophages, they must be making some signal that keeps those cells from attacking the cancer.
‘You want to find those signals so you can disrupt them and unleash the full potential of the immune system to fight the cancer.’
The team started by looking for proteins that were more highly produced in cells with cancer than those without, and found an abundance of CD24.
When they combined mixed cancer cells with macrophobes in a dish and blocked the signal, the immune cells started ‘gorging on cancer cells like they were at an all-you-can-eat buffet’.
Barkal added: ‘When we imaged the macrophages after treating the cancers with CD24 blockade, we could see that some of them were just stuffed with cancer cells.’
The researchers were particularly interested to discover that ovarian and triple negative breast cancer, which are difficult to treat, were highly affected by blocking the signalling.
They believe CD24 is the ‘dominant innate immune checkpoint’ for these cancers.
While some cancers were susceptible to attack when certain signals were blocked, some were affected by others.
They hope that most cancers will be able to be made vulnerable to attack when one or more of the signals are blocked.