Sugar molecules as a target in cancer therapy

8 Nov 2022
Sugar molecules as a target in cancer therapy

Cancer cells use sugar molecules on their surface to disable attacks by the body’s immune system.

Researchers at the University of Basel now report on how this mechanism can be neutralised.

The immune system is actually extremely well equipped to get rid of abnormal cells.

As a safety mechanism, special features are built into healthy cells so that the immune system recognises them, thus preventing a mistaken attack.

However, cancer cells sneakily manipulate these safety mechanisms in such a way that the immune system leaves them alone.

Over the past few years, immunotherapies have revolutionised cancer treatment.

These include therapies that prevent cancer cells from inhibiting the immune response.

This involves blocking what are known as “immune checkpoints” using artificially produced proteins, which allows the immune cells to successfully attack the cancer cells.

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

In the specialist journal Science Translational Medicine, his team, together with that of recent Nobel laureate Professor Carolyn Bertozzi from Stanford University, reports on a promising new approach.

By altering sugar molecules on the surface of cancer cells in mice, the researchers were able to produce a significant increase in anti-tumour immune response.

Their focus is on sugar molecules on the surface of the cancer cells, as well as on the cells in their immediate vicinity.

These particular sugars, which contain sialic acid, also occur on healthy cells, and are important for cell-to-cell communication.

However, tumours boost the proportion of these sugars on their surface.

Certain immune cells called macrophages recognise these sialic acid sugars and inadvertently turn traitor: they give other nearby immune cells the impression that all is well.

The research team’s experiments on mice have now been able to demonstrate 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 tumour coming under immunological attack.

More precise analyses have enabled the researchers to identify in mice exactly which receptor it is on the macrophages that recognises the sialic acid sugars.

If the equivalent receptor could be identified in humans, then that could be another interesting target in the bid to tackle cancer cells with the aid of the patient’s own immune system.

“The combination of our approach with the immune checkpoint blockade methods that have already been established meant we could really put the brakes on tumour growth in the laboratory mice,” says Professor Läubli.

As a next step, the researchers aim to seek ways of removing the sialic acid sugars from the tumour and its surroundings in as targeted a manner as possible, in order to avoid disrupting the function of healthy cells and eliminate side effects.

Article: Targeting cancer glycosylation repolarises tumour-associated macrophages allowing effective immune checkpoint blockade

Source: University of Basel