A second biological pathway that signals immune cells not to engulf and kill cancer cells has been identified by researchers at the Stanford University School of Medicine.
An antibody that blocks the “don’t eat me” signal has shown promise as a cancer treatment in animal models and is currently in clinical trials. Combining that antibody, known as anti-CD47, with another that blocks this newly discovered pathway could further enhance the ability of the immune system to eradicate many types of cancers, the researchers believe.
“The development of cancer cells triggers the generation of SOS molecules recognized by the body’s scavenger cells, called macrophages,” said Irving Weissman, MD, the director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, and also of its Ludwig Cancer Center. “However, aggressive cancers express a ‘don’t eat me’ signal in the form of CD47 on their surfaces. Now we’ve identified a second ‘don’t eat me’ signal and its complementary receptor on macrophages. We’ve also shown that we can overcome this signal with specific antibodies and restore the ability of macrophages to kill the cancer cells.”
A paper describing the findings will be published online Nov. 27 in Nature Immunology. Weissman, a professor of pathology and of developmental biology, shares senior authorship of the study with former postdoctoral scholar Roy Maute, PhD, who is now head of biology at Ab Initio Biotherapeutics Inc. Graduate student Amira Barkal shares lead authorship with former graduate student Kipp Weiskopf, MD, PhD, who is now a resident at Brigham and Women’s Hospital.