Improve the efficacy of cancer immunotherapy?

Nature journal highlights de Duve Institute research:
an innovative approach that could improve the efficacy of cancer immunotherapy

07/06/2023

Teams from the de Duve Institute have discovered that some molecules previously used to treat hypertension might also help the immune system to better fight cancer cells. An article published in the latest edition of the journal Nature reports on this basic research which could, in time, considerably increase the effectiveness of immunotherapy to fight a larger number of cancers.

The immune system protects the human body against disease by destroying foreign substances such as bacteria and viruses. T lymphocytes, a type of white blood cell, are the active components in this process because they recognise and destroy foreign cells. By definition, cancer cells are not foreign cells and therefore are not likely to be recognised and attacked by the T lymphocytes. However, about thirty years ago, Thierry Boon and his colleagues at the de Duve Institute and the former Brussels Branch of the Ludwig Institute for cancer Research discovered specific markers on the surface of cancer cells (called tumour antigens) that can be recognised by T cells that then destroy the cancerous cells. This work has paved the way for cancer immunotherapy, a new treatment approach that helps T lymphocytes to destroy cancerous cells. Thanks to tumour specificity and the memory of these lymphocytes, immunotherapy makes it possible to treat advanced cancers with some success. It is now used worldwide. However, it does not work in all patients or, as effectively, for all types of cancer.

New research conducted in recent years by Jingjing Zhu and her team in the laboratory of Professor Benoit Van den Eynde of the de Duve Institute and the Ludwig Institute for Cancer Research led to the publication of this article in the magazine Nature. “Immunotherapy today can effectively fight only 30% to 40% of cancers,” explains Prof. Van den Eynde. “Many cancers are resistant, largely because their T lymphocytes are not reactive enough. We discovered that drugs once used to treat hypertension could have a very interesting effect in combating these forms of immunotherapy-resistant cancers.”

These molecules have an effect on macrophages, white blood cells that engulf and digest debris from pathogens, such as cancer cells, microbes and foreign substances. They are, in a way, the human body’s waste collectors. While doing their job, these macrophages also alert the T lymphocytes of any abnormalities they encounter, raising the alarm and triggering the immune response when it is required.

Researchers at the de Duve Institute discovered that alongside their known hypotensive and anaesthetic effects, these molecules can also stimulate macrophages in their role as T-lymphocyte informants, making T lymphocytes more reactive and more effective at rejecting cancer cells, particularly in cancer models resistant to standard immunotherapy. This new approach could therefore “boost” the clinical immunotherapy process, particularly for the many cases of cancer for which this treatment is still of limited effectiveness.

These promising results call for additional research to find new molecules that might allow clinical trials to validate new treatments likely to offer enormous hope to patients suffering from cancers for which immunotherapy is currently not effective. “One could imagine using existing blood pressure-lowering drugs,” explains Prof. Van den Eynde. “But it would be quite risky, owing to the undesired effects and the toxicity of these drugs at the necessary doses. Another approach is to develop new molecules that would act in the same way on macrophages, but would not have the unwanted toxic effects. We have already made significant progress in this direction.”

Article describing this research

Tumour immune rejection triggered by activation of α2-adrenergic receptors
Zhu J, Naulaerts S, Boudhan L, Martin M, Gatto L & Van den Eynde BJ
Nature (2023), doi: 10.1038/s41586-023-06110-8

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