A major advance in the understanding of brain tumors

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Brain metastasis tissue showing immune cells in blue, neutrophils in pink and bl
Brain metastasis tissue showing immune cells in blue, neutrophils in pink and blood vessels in yellow. Photo: Roeltje Maas, Pre Johanna Joyce’s lab
Researchers at the Department of Oncology (UNIL-CHUV) have published an in-depth analysis in the prestigious journal "Cell", shedding light on the hitherto unknown functions of neutrophils in brain tumor environments.

Brain tumors remain one of the most complex medical challenges of our time, affecting thousands of lives every year. This is due in particular to the complexity of the cells and tissues making up the brain, and the heterogeneity of brain tumors (primary or metastatic). With this in mind, a team from the Department of Oncology (UNIL-CHUV), the Lausanne branch of the Ludwig Institute and their collaborators from the CHUV, the Swiss Institute of Bioinformatics and several Spanish research institutes, are shedding new light on neutrophils, immune cells abundant in the circulation, and their essential roles within these particularly complex tumours.

Researchers unveil, in the September 27, 2023 issue of Cell, an in-depth analysis highlighting the previously unknown functions of neutrophils in brain tumor environments. Neutrophils, abundant immune cells in the bloodstream and well-known for their presence in tumors, are attracting considerable scientific interest for their precise roles in various types of cancer, particularly in the microenvironment of brain tumors.

Unravelling the mystery: neutrophils in brain tumours

The research team, led by Prof. Johanna Joyce, full professor in the Faculty of Biology and Medicine at UNIL, has embarked on an extensive multimodal investigation of neutrophils present in the tumor tissue of patients with glioma (primary tumor) and brain metastases (metastatic tumor originating from various primary cancers), comparing their findings with matched peripheral blood samples. This pioneering study represents the first in-depth exploration of neutrophil phenotypes and functions in these brain tumors.

Distinct neutrophil characteristics: key findings

Using advanced profiling strategies on both human samples and sophisticated mouse models to track neutrophil behavior in vivo, the researchers made a remarkable discovery: neutrophils associated with brain tumors (TANs) display distinctive characteristics significantly different from those of blood neutrophils. These TANs have a prolonged lifespan, immunosuppressive properties and pro-angiogenic capacity, revealing crucial information about their functions within brain tumor environments.

The inflammatory signature of NATs

Further analysis of NATs revealed a unique inflammatory signature, influenced by a combination of soluble pro-inflammatory mediators including TNF-E and ceruloplasmin. The study also highlighted variations in this signature between NATs from brain metastases and glioma, highlighting the importance of understanding the nuances of neutrophil behavior in different types of brain tumors.

Myeloid cells at the heart of the matter: implications for immunity against brain tumors

Furthermore, the research highlights the central role of myeloid cells, including tumor-associated macrophages, in orchestrating a network of pro-inflammatory mediators within the brain tumor environment. This discovery supports the concept of a critical myeloid niche regulating global immune suppression in human brain tumors.

Prospects and potential therapeutic strategies

These findings represent a significant leap forward in our understanding of the functions of neutrophils within the complex landscape of brain tumors", said Roeltje Maas , PhD student in Johanna Joyce’s laboratory at the UNIL-CHUV Department of Oncology and first author of the study. Our research lays the foundations for future therapeutic strategies aimed at modulating these unique neutrophil populations to improve treatment efficacy for patients with brain tumors," adds Johanna Joyce.

A catalyst for progress in brain tumour research

This landmark research not only expands our knowledge of neutrophil function, but also lays the groundwork for potential breakthroughs in cancer treatment, particularly for patients with brain tumors.

This study was supported by Ludwig Cancer Research, an SNSF Advanced Grants subsidy, the University of Lausanne, the Breast Cancer Research Foundation, the Carigest Foundation, the ISREC Foundation, the Swiss Bridge Award, the Austrian Science Fund, the Leenaards Foundation, the European Molecular Biology Organization, the Junta de Comunidades de Castilla-La Mancha, the Human Frontier Science Program, the European Commission, the MCIN and the Pro CNIC Foundation.