Enzyme Prevents Cancer Cells from Hiding from Immune System

Researchers from University of Basel and Stanford University report a strategy to neutralize the ability of cancer cells to hide themselves from the immune system. The findings could boost response rates to immunotherapies, which have revolutionized cancer treatment in recent years but have demonstrated limited success in certain cancer types.

“With many tumors… there have only been modest levels of success. That’s why we’re looking for new approaches to engage anti-tumor immune responses more efficiently,” says Professor Heinz Läubli from the Department of Biomedicine at the University of Basel and the University Hospital Basel.

Though well-equipped to get rid of abnormal cells, the immune system has a safety mechanism that prevents it from mistakenly attacking healthy cells. Unfortunately, cancer cells can manipulate these mechanisms in such a way that the immune system leaves them alone.  

Surface sugar molecules containing sialic acid are one tool cancer cells use to hide. Though such sugars occur on healthy cells and are important for cell-to-cell communication, they are present in higher proportions on cancer cells. Macrophages recognize these sialic acid sugars and inadvertently tell nearby immune cells that all is well.

Läubli and colleagues, who include recent Nobel laureate and Stanford University Professor Carolyn Bertozzi, were able to show in mice that the sialic acid sugars can be removed, or at least very much reduced, with the help of an enzyme. This means that the macrophages no longer prevent the tumor coming under immunological attack. By altering the sugar molecules on the surface of the cancer cells and cells in the immediate vicinity, they were able to produce a significant increase in anti-tumor response.

The team was also able to identify in mice exactly which receptor it is on the macrophages that recognizes sialic acid sugars. If the equivalent receptor could be identified in humans, then that could be another interesting target for leveraging a patient’s own immune system against cancer cells.

Läubli says the strategy is also complementary to existing immunotherapies that block “immune checkpoints” using artificially produced proteins. “The combination of our approach with the immune checkpoint blockade methods that have already been established meant we could really put the brakes on tumor growth in the laboratory mice,” says Professor Läubli.

Future work will seek ways to remove the sialic acid sugars from the tumor and its surroundings in as targeted a manner as possible to avoid disrupting the function of healthy cells and eliminate side effects. The work is described in a recent issue of Science Translational Medicine.