‘Don’t Eat Me’ Signal May Be Key to Cancer Therapies, Finds New Study

Researchers at the Stanford University School of Medicine have discovered yet another new signal that may be key to developing novel cancer therapies. The discovery consists of a new “don’t eat me” signal that some cancers seem to use to evade destruction by the immune system. 

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Research has already shown that blocking these pesky signals in mice implanted with human cancers sees immune cells (macrophages) attack and eliminate the cancers. The way this process function is that, in healthy cells, proteins on their surface can tell macrophages not to destroy them.

But in cancer cells, the same system is used to evade detection by macrophages. The proteins discovered so far that are used by cancer cells to thrive are the PD-L1, CD47, and the beta-2-microglobulin subunit of the major histocompatibility class 1 complex.

A new protein added to the list

Researchers are already looking into antibodies that block CD47 in clinical trials as well as cancer treatments that target PD-L1 in the clinic. Now, there may be a new protein to add to this list.

The newly-discovered protein is called CD24, and it also acts as a “don’t eat me” signal by cancer cells.

“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,” said senior author Irving Weissman, MD, professor of pathology and of developmental biology and director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Research.

This latest protein was discovered when researchers began investigating proteins that were produced more highly in cancers than in the tissues from which the cancers arose.

“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,” said lead author Amira Barkal, an MD-PhD student. “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 researchers ran several tests that all showed that when CD24 signaling was blocked, the macrophages were free to eat up the cancer cells. “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,” Barkal said. 

Complementary to CD47

Furthermore, the scientists uncovered that CD24 signaling often seemed to operate in a complementary way to CD47 signaling. Some cancers, such as blood cancers, responded to CD47 blocking, but not to CD24 blocking. Other cancers, such as ovarian cancer, had the opposite effect.

The researchers now hope that most cancers can be treated by blocking either one of these signals or all together. “There are probably many major and minor ‘don’t eat me’ signals, and CD24 seems to be one of the major ones,” Barkal said

A study describing the research was published in the journal Nature.