TREM2-Expressing Multinucleated Giant Macrophages Are a Biomarker of Good Prognosis in Head and Neck Squamous Cell Carcinoma
Gessain G, Anzali AA, Lerousseau M, Mulder K, Bied M, Auperin A, Stockholm D, Signolle N, Sassi F, Marques Da Costa ME, Marchais A, Sayadi A, Weidner D, Uderhardt S, Blampey Q, Nakkireddy SR, Broutin S, Dutertre CA, Busson P, Walter T, Marhic A, Moya-Plana A, Guerlain J, Breuskin I, Casiraghi O, Gorphe P, Classe M, Scoazec JY, Blériot C, Ginhoux F (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 14
Pages Range: 2352-2366
Journal Issue: 12
DOI: 10.1158/2159-8290.CD-24-0018
Abstract
Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type of macrophages—in tumors from patients with HNSCC, which are associated with a favorable prognosis in treatment-naive and preoperative chemotherapy–treated patients. Importantly, MGC density increased in tumors following preoperative therapy, suggesting a role of these cells in the antitumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantifi-cation on routinely stained pathological whole slide images. Finally, we used spatial transcriptomic and proteomic approaches to describe the MGC-related tumor microenvironment and observed an increase in central memory CD4 T cells. We defined an MGC-specific signature resembling to TREM2-expressing mononuclear tumor-associated macrophages, which colocalized in keratin tumor niches. Significance: Novel individual biomarkers are needed to guide therapeutic decisions for patients with head and neck cancer. We report for the first time, granulomas of TREM2-expressing multinucleated giant macrophages in keratin-rich tumor niches, as a biomarker of favorable prognosis and developed a deep-learning model to automate its quantification on routinely stained pathological slides.
Authors with CRIS profile
Involved external institutions
Institut Gustave-Roussy
France (FR)
Mines ParisTech / École Nationale Supérieure des Mines de Paris (ENSMP)
France (FR)
PSL Research University / Université de recherche Paris Sciences et Lettres
France (FR)
Analyse Moléculaire, Modélisation et Imagerie de la Maladie Cancéreuse (AMMICA)
France (FR)
Université Sorbonne Paris Cité
France (FR)
Université Paris-Saclay
France (FR)
Mayo Clinic Hospital
United States (USA) (US)
France (FR)
Mines ParisTech / École Nationale Supérieure des Mines de Paris (ENSMP)
France (FR)
PSL Research University / Université de recherche Paris Sciences et Lettres
France (FR)
Analyse Moléculaire, Modélisation et Imagerie de la Maladie Cancéreuse (AMMICA)
France (FR)
Université Sorbonne Paris Cité
France (FR)
Université Paris-Saclay
France (FR)
Mayo Clinic Hospital
United States (USA) (US)
How to cite
APA:
Gessain, G., Anzali, A.A., Lerousseau, M., Mulder, K., Bied, M., Auperin, A.,... Ginhoux, F. (2024). TREM2-Expressing Multinucleated Giant Macrophages Are a Biomarker of Good Prognosis in Head and Neck Squamous Cell Carcinoma. Cancer Discovery, 14(12), 2352-2366. https://doi.org/10.1158/2159-8290.CD-24-0018
MLA:
Gessain, Grégoire, et al. "TREM2-Expressing Multinucleated Giant Macrophages Are a Biomarker of Good Prognosis in Head and Neck Squamous Cell Carcinoma." Cancer Discovery 14.12 (2024): 2352-2366.
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