Immune cells called macrophages can gobble up cancer cells and initiate an anti-cancer immune response. Cancer cells, for their part, often express proteins that tell macrophages not to do so. Ludwig Stanford Director Irv Weissman’s lab has previously discovered a couple of such proteins, and an antibody he and his team developed to block one of them, CD47, is today in clinical trials as a cancer therapy. In August, Irv and his colleagues reported in Nature their discovery that the protein CD24 transmits yet another “don’t eat me” signal to macrophages and that it too appears to be used by certain cancer cells to protect themselves. Macrophages sense the CD24 signal through a receptor called SIGLEC-10. Blocking that interaction prompted macrophages to get back to their cancer cell repast and, in mice implanted with human breast tumors, induced tumor regression and extended the survival of the mice. Tough-to-treat ovarian and triple-negative breast cancers were especially vulnerable to such intervention. Notably, Irv and his team also found that cancers that resist CD47 blockade are susceptible to CD24 blockade—and vice versa—suggesting either or both antibodies might cover treatment of a broad spectrum of cancer types.
This article appeared in the November 2019 issue of Ludwig Link. Click here to download a PDF (1 MB).