Researchers have discovered a common mechanism that allows both cancer and pregnancy to evade the immune system.
This breakthrough could lead to new ways to treat cancer by harnessing the body’s natural defenses.
During pregnancy, the immune system does not reject the growing fetus due to specific mechanisms in the placenta. Similarly, tumors avoid immune rejection using comparable strategies.
Dr. Weiping Zou from the University of Michigan Rogel Cancer Center explains, “In pregnancy, it’s a good thing that the immune system tolerates the fetus.
But in cancer, it means the tumor grows unchecked, making treatments that stimulate an immune response less effective.”
To explore this connection, Zou and his colleagues combined their expertise in immunology, cancer genetics, gynecologic pathology, and medicinal chemistry.
They identified a molecular mechanism, called B7-H4, that suppresses the immune system in both pregnancy and cancer. By blocking B7-H4, the immune system can fight the cancer more effectively.
Their findings, published in the journal Cell, revealed that the hormone progesterone regulates the B7-H4 immune checkpoint.
This discovery was made using mouse models and cell lines of breast and gynecologic cancers. Previously, B7-H4 was linked to shorter survival in cancer patients, but this is the first time progesterone’s role in immune response to cancer has been highlighted.
The researchers tested an inhibitor to block progesterone signaling in mice with breast cancer and in human breast cancer tissue samples. This approach slowed the cancer’s growth in mice and activated the immune response, though the effect was clear but not dramatic.
“B7-H4 is an important checkpoint, but it’s complicated,” said Zou. “Progesterone regulation is one mechanism, but we need more studies to understand other mechanisms that may regulate B7-H4. We do not yet have a direct way to block this pathway since the receptors remain unknown.”
The research team plans further studies to understand how B7-H4 protein stability is regulated and to explore other factors involved in cancer immunology. This ongoing research could pave the way for new treatments that improve cancer patients’ outcomes by enhancing the immune system’s ability to fight tumors.
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