Researchers at the Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute in Australia have discovered that MR1 proteins may help cancer cells hide from our immune system. MR1 are major histocompatibility complex (MHC) class I-related proteins that bind themselves to T-cells.
MR1-restricted T-cells are also called mucosal-associated invariant T (MAIT) cells and are associated with several immune responses against a variety of pathogens. These MAIT cells normally regulate and inform our T and NK cells and tell them when to attack disease or sickness within our bodies.
MR1-restricted T-cells contribute to autoimmune and inflammatory diseases, lupus, rheumatoid arthritis, and diabetes.
During their study, the team at QIMR discovered that if MAIT cells were turned on, they could prevent NK and T-cells from attacking tumors. However, cancer tumors can also turn on the MAIT cells by displaying the MR1 molecules on their surface. This, in turn, blocks the T and NK cells from identifying the cancer cells, allowing cancer to grow. The study was published in Cancer Discovery.
Michele Teng, senior researcher on the study, says, “The cancer is effectively creating its own defense mechanism to evade immune attack and survive, The display of MR1 activates the MAIT cells, which in turn switch off cancer-fighting T and NK cells. While other regulatory cells of the immune system are known to stop T and NK cells from killing tumor cells, this is the first time it’s been shown that these regulatory MAIT cells can do this job.”
This is a big discovery because this could help lead to new treatments in immunotherapy. The team administered antibodies to mice that blocked MR1, and it ended up working. It prevented the MAIT cells from turning on, increased the abilities of the T and NK cells, and slowed the growth and spreading of new cancer cells.
Teng continues, “This work demonstrates that antibodies that block MR1 could in the future be an effective new immunotherapy. It probably won’t work on every cancer, but it looks like it could be effective in treating cancers that can display the MR1 molecule. It also means this display of MR1 could be used to screen which patients would respond to this immunotherapy.”
The next step from here for the researchers is to try this test on humans and determine which types of cancer this will work on and which cancers use MR1. This type of testing could also be helpful for diseases like lupus, where the immune system attacks itself. Detecting cancer’s hiding tricks is now informing treatment design too: UCLA’s engineered cord blood T cells carry a backup receptor system built to catch tumors that hide their targets.
