Fight Aging!

Cancer cells abuse signals used elsewhere in normal mammalian biochemistry to prevent immune cells from destroying other cells, such as CD47. Interfering in these "don't eat me" signals has produced significant gains in the development of effective cancer therapies that can target multiple types of cancer. Here, researchers describe a newly discovered "don't eat me" signal, CD24, that should allow this class of cancer therapy to be expanded to target cancers that have proved resilient to existing implementations. This and related lines of work that lead to more general anti-cancer platforms are one of the reasons why young people today should have little concern over cancer in their old age yet to come. It will be near entirely a controllable condition, treated efficiently with few side effects, by mid-century.

Normally, immune cells called macrophages will detect cancer cells, then engulf and devour them. In recent years, researchers have discovered that proteins on the cell surface can tell macrophages not to eat and destroy them. This can be useful to help normal cells keep the immune system from attacking them, but cancer cells use these "don't eat me" signals to hide from the immune system. Researchers had 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. Cancer treatments that target PD-L1 or the PDL1 receptor are being used in the clinic.

Researchers now report they have found that a protein called CD24 also acts as a "don't eat me" signal and is used by cancer cells to protect themselves. "Finding that not all patients responded to anti-CD47 antibodies helped fuel our research to test whether non-responder cells and patients might have alternative 'don't eat me' signals. "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 search showed that many cancers produce an abundance of CD24 compared with normal cells and surrounding tissues. In further studies, the scientists showed that the macrophage cells that infiltrate the tumor can sense the CD24 signal through a receptor called SIGLEC-10. They also showed that if they mixed cancer cells from patients with macrophages in a dish, and then blocked the interaction between CD24 and SIGLEC-10, the macrophages would start gorging on cancer cells. Lastly, they implanted human breast cancer cells in mice. When CD24 signaling was blocked, the mice's scavenger macrophages of the immune system attacked the cancer. Of particular interest was the discovery that ovarian cancer and triple-negative breast cancer, both of which are very hard to treat, were highly affected by blocking the CD24 signaling.

The other interesting discovery was that CD24 signaling often seems to operate in a complementary way to CD47 signaling. Some cancers, like blood cancers, seem to be highly susceptible to CD47-signaling blockage, but not to CD24-signaling blockage, whereas in other cancers, like ovarian cancer, the opposite is true. This raises the hope that most cancers will be susceptible to attack by blocking one of these signals, and that cancers may be even more vulnerable when more than one "don't eat me" signal is blocked.

Link: http://med.stanford.edu/news/all-news/2019/07/new-dont-eat-me-signal-may-provide-basis-for-cancer-therapies.html