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Could unknown immune cell receptors explain why immunotherapy doesn’t always work?

KWF/Alpe d’HuZes funds fundamental research into a potential new ‘brake on the immune system

Why does immunotherapy work for some cancer patients but not for others? Researchers at UMC Utrecht aim to find out if so-called multispanners (MIRs) might play a role. “We want to know whether MIRs act as brakes on the immune system. If that’s the case, we may be able to improve immunotherapy for more patients,” says project leader Michiel van der Vlist, assistant professor and principal investigator at the Inhibitory Receptor Lab, Center for Translational Immunology (UMC Utrecht).

MIRs are a recently discovered group of proteins found on immune cells. Some of these proteins may inhibit immune responses in the tumor environment, potentially reducing the effectiveness of immunotherapy. This therapy helps activate the immune system to fight cancer.

KWF/Alpe d’HuZes is funding this fundamental research, which builds on earlier work by Saskia Vijver, PhD candidate researching inhibitory receptors in cancer at UMC Utrecht. The study is conducted at the Inhibitory Receptor Lab. The researchers are focusing on two key immune cells targeted by immunotherapy: T cells and macrophages. Using techniques such as CRISPR/Cas9, they will investigate if disabling MIRs affects the function of these cells.

The study will use models of pancreatic and colorectal cancer, two cancer types where immunotherapy is not yet highly effective. The research may offer new insights into how the immune system behaves in cancer and why current treatments don’t work for everyone.

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