Ovarian cancer and triple-negative breast cancer are among the most deadly diseases affecting women. There is almost no targeted therapy and the metastatic rate is very high. Often, cancer cells express a "don't eat me" signal to evade the identification and attack of immune cells. In cancer immunotherapy, most cancer cells are attacked by one of the signals being blocked. When more than one "Don't Eat Me" signal is blocked, they will become more vulnerable to destruction.
Recently, the team of stem cell research and the team of Professor Irving Weissman of Stanford University in the United States have discovered a new "Don't Eat Me" signal, which brings new targets for cancer immunotherapy. The research has recently been published in Nature.
Scientists have shown that blocking this signal in mice implanted with human cancer allows their immune cells to attack cancer cells, and blocking other "don't eat me" signals has become the basis of other anticancer therapies.
Previous studies have shown that PD-L1, CD47 and β-2-microglobulin subunits are used by cancer cells to protect themselves from immune cell attack. Blocking anti-CD47 mAb is in clinical trials. Cancer therapies targeting PD-L1 or PDL1 receptors have been used clinically.
In this new study, Stanford's research team discovered that a protein called CD24 can also be used as a "don't eat me" signal and is used by cancer cells to protect itself.
Irving Weissman, the study's co-author, director of the Stanford University's Institute of Stem Cell Biology and Regenerative Medicine, and head of the Cancer Center for Cancer Stem Cell Research and Medicine, and a well-known professor of cancer clinical research, said: "Not all patients respond to CD47 antibodies. A discovery prompted us to further study to test whether non-responsive cells and patients may have an alternative 'don't eat me' signal."
Looking for other signals
In this study, scientists first sought to produce more protein in cancer cells than in normal tissues. Amira Barkal, the first author of the study, said: "We know that if cancer cells grow in the presence of macrophages, they will send out some kind of signal that prevents these cells from attacking themselves. We need to find these signals to intervene. They and release the full potential of the immune system to fight cancer."
Studies have shown that cancer cells produce large amounts of CD24 compared to normal cells and surrounding tissues. In further research, the scientists found that tumor-infiltrating macrophages can sense CD24 signaling through a receptor called Siglec-10. They also found that if the patient's cancer cells are mixed with macrophages in a culture dish and then block the interaction between CD24 and SIGLEC-10, the macrophages will devour the cancer cells as if they were eating a buffet. . Barkal said: "When we treated the cancer with CD24 blocker, we observed macrophages and found that they were filled with cancer cells."
Finally, the team implanted human breast cancer cells into mice and observed that when CD24 signaling is blocked, macrophages in the mouse immune system begin to attack cancer cells.
Of particular interest to the researchers is that both refractory ovarian cancers and triple-negative breast cancers are significantly affected by the blockade of CD24 signaling. "CD24 can be a major innate immune checkpoint in ovarian and breast cancer and is a promising target for cancer immunotherapy," Barkal said.
Complementary to CD47?
Another interesting finding is that CD24 signals usually complement the CD47 signal. Some cancers, such as blood cancer, appear to be highly sensitive to CD47 signaling block, but are not sensitive to CD24 signaling blockers; in other cancers, such as ovarian cancer, the opposite is true. This brings hope to cancer treatment, that is, most cancers are attacked because one of the signals is blocked. When more than one "Don't Eat Me" signal is blocked, then cancer cells will become easier. be destroyed.
Barkal said: "There may be many major and minor ‘don't eat me’ signals, and CD24 seems to be one of the main signals.”
Researchers now hope that therapies that block CD24 signaling can follow the footsteps of anti-CD47 therapy, first in a preclinical trial for safety testing, and then in clinical trials of human safety and efficacy.
For Weissman, the discovery of the second “Don't Eat Me” signal validates a scientific approach that combines basic research with clinical research. Weissman said: "CD47 and CD24 were discovered by Stanford University doctors and other researchers. These were initially basic findings, but their connection to cancer and cancer cells evading macrophages led the research team. Beginning preclinical testing. This shows that combining research with medical training can accelerate the acquisition of potentially new life-saving discoveries." [Reprinted Source: China Biotechnology Network]