THE ESSENTIAL
- A team from Gustave Roussy discovered that the presence of macrophages expressing TREM2 is a good prognosis factor in ENT squamous cell carcinomas, information that could improve patient care.
- “The results of this work show that high levels of multinucleated giant cells are associated with better overall survival and longer survival without disease progression.”
- The team was able to extend this discovery to other non-ENT squamous cell carcinomas such as squamous cell carcinomas of the cervix and would like to verify whether this is also the case for squamous cell carcinomas of the esophagus, lung or even of the skin.
Squamous cell carcinoma is the most common type of cancer in ENT, accounting for approximately 90% of cases. It develops from the mucous membranes of the mouth, tonsils, pharynx or larynx. “Approximately 50% of patients affected by this pathology experience recurrence or distant metastasis within three years of diagnosis.”, notes the Gustave Roussy Institute in a press release. However, by 2030, specialists estimate that there will be 1.08 million new cases per year in the world… Hence the urgency of improving therapeutic care!
“High levels of multinucleated giant cells are associated with better overall survival”
“During my internship in ENT anatomopathology at Gustave Roussy, I took care of numerous patients suffering from ENT squamous cell carcinomas, whose microscopic analysis of their surgical specimen revealed the presence of large cells easily identifiable by their size, multinucleated giant cells, explains Grégoire Gessain, pathology intern at Gustave Roussy. Until now, no study had been carried out to determine whether or not their presence had an impact on the prognosis of patients. This is how this research project began, which mobilized numerous professionals present at Gustave Roussy: anatomopathologists, surgeons and immunologists, making it possible to carry out real translational research work.”
To carry out the research, scientists studied two cohorts for a total of 394 patients with ENT squamous cell carcinomas. The results of this work, published in the journal Cancer Discovery, demonstrate that in the case of squamous cell carcinoma of the head and neck, the presence of a number of multinucleated giant cells is a good prognosis factor. These cells come from the fusion of two types of cells of the immune system: monocytes and macrophages. These are formed “in response to keratin produced in an anarchic manner by cancer cells in order to phagocytize it, or destroy it by ingesting it”, indicates the press release.
“The results of this work show that high levels of multinucleated giant cells are associated with better overall survival and longer survival without disease progression. Results that were found to be independent of other factors such as gender, age, disease stage, smoking and alcohol consumption”, specifies Gustave Roussy.
“MAcrophages expressing TREM2 are a good prognosis factor in squamous cell carcinomas”
“Thanks to spatial transcriptomics, a cutting-edge technology that makes it possible to characterize cells directly in their tumor microenvironment on histology slides, we were able to confirm the macrophage nature of multinucleated giant cells. These giant cells express TREM2, a membrane protein that promotes the process of phagocytosis by macrophages”, explains Professor Florent Ginhoux, head of the laboratory where the research was carried out. This news is all the more surprising given that previous work had concluded that the presence in the tumor environment of macrophages expressing TREM2 was a poor prognosis factor. “No one had actually been interested in the link between these cells and the type of cancer in which they develop. We demonstrate that TREM2-expressing macrophages are a good prognosis factor in squamous cell carcinomas. But the prognostic value is completely reversed in the majority of adenocarcinomas.”, underlines Grégoire Gssaisin.
Next step? Validate that this biomarker still has a good prognosis in cohorts from other centers in France and internationally, then determine its clinical use. “Finding a reliable and reproducible prognostic biomarker is something absolutely essential in oncology: it helps clinicians stratify patients according to their risk and individualize treatments. For example, reducing intensity and toxicities in low-risk patients, or intensifying treatments in high-risk patients to improve the chance of recovery. But also, helping to improve patient selection for clinical trials in the future”, indicates Dr Philippe Gorphe, ENT surgeon at Gustave Roussy.
A discovery extended to other non-ENT squamous cell carcinomas
The team was also able to extend this discovery to other non-ENT squamous cell carcinomas such as cervical squamous cell carcinomas, where the results on the influence of giant cell density were confirmed. Other research should also be organized for squamous cell carcinomas of the esophagus, lung and even the skin.
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