A recent discovery from the Montreal Clinical Research Institute (IRCM) sheds new light on the complexity of the immune system and its role in cancer treatment. The study, published in Science Immunology, highlights how a deeper understanding of immune “brakes” could lead to more effective therapies.
The immune system uses built-in mechanisms—known as inhibitory immune checkpoints—to prevent attacks on healthy cells. While they are essential for maintaining balance, these checkpoints can also prevent the immune system from attacking cancer cells. To counter this, scientists have developed checkpoint blockers, a class of drugs that release these brakes and help the immune system fight cancer. However, these treatments don’t work for all patients or all types of cancer.
“Checkpoint pathways are far more complex than we once thought,” explains Dr. Zhenghai Tang, lead author of the study and former researcher in Dr. André Veillette’s lab at the IRCM, now based at the University of Macau. “To improve treatments, we need to understand how these brakes function at a molecular level.”
The study focused on two key checkpoint molecules: SIRPα, found on immune cells called macrophages, and CD47, present on many cells including cancer cells. When these two molecules interact, they send a “don’t eat me” signal that prevents macrophages from destroying cancer cells.
By blocking the interaction between SIRPα and CD47, the researchers were able to reduce the inhibitory signal by about 50%. Surprisingly, the remaining half of the signal persisted even without CD47—suggesting that SIRPα can suppress immune responses through other pathways.
This finding helps explain why therapies targeting CD47 alone have shown limited success. “To make these treatments more effective,” says Dr. Tang, “we may need to block all the ways SIRPα suppresses the immune system—not just its link to CD47.”
The implications of this research are significant. It underscores the need for:
- A better understanding of how checkpoint molecules behave and interact.
- More precise drug design, including monoclonal antibodies.
- Improved translation of findings from animal models to human biology.
As scientists continue to unravel the intricacies of immune regulation, discoveries like this pave the way for safer, smarter, and more personalized cancer therapies.
