Newly discovered “don’t eat me” signal shows potential for ovarian and triple-negative breast cancer treatment

Stanford researchers have found that cancer cells have a protein called CD24 on their surface that enables them to protect themselves against the body’s immune cells.
Courtesy of Shutterstock

Getting a breast cancer diagnosis is devastating news in and of itself. Currently, there are treatment options that target three different types of receptors, which are named hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR), commonly found in breast cancer cells, . Unfortunately, in triple-negative breast cancer, which occurs in 10-20% of breast cancer cases, all three receptors are absent, making this form of breast cancer very aggressive and difficult to treat.

In recent years, researchers have discovered that proteins on the cell surface can tell macrophages, an immune cell designed to detect and engulf foreign or abnormal cells, not to eat and destroy them. This can be useful to help normal cells keep the immune system from attacking them, but cancer cells can also use these “don’t eat me” signals to hide from the immune system. 

An illustration of a macrophage, a vital part of the immune system, engulfing and destroying a cancer cell. Antibody 5F9 blocks a “don’t eat me” signal emitted from cancer cells. Courtesy of Forty Seven, Inc.

In fact, because of this concept, a CIRM-funded clinical trial is being conducted that uses an antibody called 5F9 to block a “don’t eat me” signal known as CD47 that is found in cancer cells. The results of this trial, which have been announced in a previous blog post, are very promising.

Further building on this concept, a CIRM-funded study has now discovered a potential new target for triple-negative breast cancer as well as ovarian cancer. Dr. Irv Weissman and a team of researchers at Stanford University have discovered an additional “don’t eat me” signal called CD24 that cancers seem to use to evade detection and destruction by the immune system.

In a press release, Dr. Weissman talks about his work with CD47 and states that,

“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.” 

The scientists began by looking for signals that were produced more highly in cancers than in the tissues from which the cancers arose. It is here that they discovered CD24 and then proceeded to implant human breast cancer cells in mice for testing. When the CD24 signaling was blocked, the mice’s immune system attacked the cancer cells.

An important discovery was that ovarian and triple-negative breast cancer were highly affected by blocking of CD24 signaling. The other interesting discovery was that the effectiveness of CD24 blockage seems to be complementary to CD47 blockage. In other words, some cancers, like blood cancers, seem to be highly susceptible to blocking CD47, but not to CD24 blockage. For other cancers, like ovarian cancer, the opposite is true. This could suggest that most cancers will be susceptible to the immune system by blocking the CD24 or CD47 signal, and that cancers may be even more vulnerable when more than one “don’t eat me” signal is blocked.

Dr. Weissman and his team are now hopeful that potential therapies to block CD24 signaling will follow in the footsteps of the clinical trials related to CD47.

The full results to the study were published in Nature.

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