July 31, 2019, New York—Researchers led by Ludwig Stanford Director Irv Weissman have discovered a new signal that cancers seem to use to evade detection and destruction by the immune system. Blocking this signal in mice implanted with human cancers allows immune cells to attack the cancers.
Immune cells called macrophages can detect, engulf and devour cancer cells. In recent years, researchers have discovered that proteins on the cell surface can tell macrophages not to do so. This protects healthy cells from immune attack, but cancer cells often exploit such signals to evade immune responses. Weissman and his colleagues previously discovered that one such protein, CD47, is frequently used by cancer cells to thwart macrophage attack, and an antibody they developed to block CD47’s “don’t-eat-me” signal is today in clinical trials as a cancer therapy.
Weissman and his colleagues now report that a protein called CD24 transmits a distinct “don’t eat me” signal to macrophages and that it too appears to be used by certain cancer cells to protect themselves. A paper describing the research appears in the current issue of Nature.
“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 Weissman, who is also professor of pathology and of developmental biology at the Stanford University School of Medicine and director of the Institute for Stem Cell Biology and Regenerative Medicine.
Weissman’s team found that many cancers produce an abundance of CD24 compared with normal cells and surrounding tissues, and that macrophages in tumors sense its signal through a receptor called SIGLEC-10. Blocking that interaction in tissue cultures prompted macrophages to start gorging on cancer cells. When CD24 signaling was similarly blocked in mice implanted with human breast cancer cells, their macrophages attacked the cancer. Notably, ovarian and triple-negative breast cancer, which are very hard to treat, were particularly susceptible to CD24 blockade.
The researchers further found that CD24 signaling often operates in a complementary way to CD47 signaling. Some cancers, like blood cancers, seem to be highly susceptible to CD47 blockade, but not to CD24 blockade, whereas in other cancers, like ovarian cancer, the opposite is true. This suggests that most cancers may be susceptible to the blockade of one of these signals, and that many may be even more susceptible to the blockade of both.
More on these findings is available in the Stanford release from which this summary is derived.
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Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for more than 40 years. Ludwig combines basic science with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Since 1971, Ludwig has invested $2.7 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit www.ludwigcancerresearch.org.
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