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Of macrophages, mice and men…

Augustus 29, 2019 |
Professor Stanislas Goriely has been awarded a grant as part of the WIN²WAL programme for his ambitious research project in immuno-oncology. At the heart of the project are ‘humanised’ mice that will help the researchers better understand the strange behaviour of macrophages in the tumour environment.

Ordinarily, macrophages act as sentinels: they spot pathogenic agents (viruses, bacteria, etc.), and are also involved in wound healing as they trigger restorative mechanisms.

When macrophages ‘betray’ us

In the context of cancer, however, macrophages appear to ‘switch sides’. ‘Of all immune cells, macrophages are probably those that have the closest interactions with tumour cells’, explains Professor Stanislas Goriely, senior research associate with FNRS at the Institute for Medical Immunology. ‘And the presence of many macrophages in the tumour environment is generally associated with a poorer prognosis. This is because macrophages promote angiogenesis(1) and, therefore, tumour growth. They also appear to block response to treatment, especially immunotherapy.’
Understanding how and why macrophages behave this way is a major challenge for research.

Humanised mice: ‘HumaMice’

Researchers have long been confronted with a major hurdle: ‘In addition to the heterogeneity that exists within species, there are significant differences between human and mouse macrophages’, continues Professor Goriely. ‘Many phenomena observed in mice cannot be transposed to humans.’
A few years ago, researchers at Yale University (USA) created transgenic mice by replacing some of their genes with human genes that code for the growth factors that are necessary to the development of immune cells. This enabled the mice to recreate a functional immune system when they were implanted with human stem cells. These ‘humanised’ mice are much closer to human clinical subjects, and open up fascinating perspectives for research in immuno-oncology.

HumaMice at the Biopark

With the WIN²WAL grant it has been awarded, Professor Goriely’s team will use these models at the Biopark. 'In collaboration with the de Duve Institute at UCLouvain, we will develop tumour models in these mice, thus recreating a human tumour micro-environment made up of tumour cells and immune cells (including macrophages). Our goal is to study the interactions between tumour cells and macrophages, but also between macrophages and other immune cells.'
The industrial partner of the project is iTeos Therapeutics. This company, based on the BioPark, is especially focusing on the tumor microenvironment to identify new therapteutic targets. The complementarity of expertise and the convergence of scientific motivations naturally led iTeos to support this project.

Research questions and final goal

The research programme, called ‘HumaMice’, pursues multiple objectives, including:
  • defining the various populations of macrophages;
  • validating certain genes (as potential therapeutic targets) linked to immunosuppressive activity;
  • identifying and understanding the signals that tumour cells send to macrophages.
Ultimately, the goal is to find a way to properly reprogram macrophages, which would deprive tumours of a valuable ally.

Notes:
(1) Angiogenesis is the formation of small blood vessels inside the tumour.
(2) The ‘HumaMice’ project has received 1.2 million euros in funding for a period of four years.

Candice Leblanc