Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma

Menée à l'aide d'images de lames histologiques, d'un modèle d'apprentissage automatique ainsi que d'analyses transcriptomiques et protéomiques d'échantillons tumoraux issus de patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude met en évidence une association entre la densité intratumorale de macrophages géants multinucléés exprimant la protéine membranaire TREM2 et un pronostic favorable

Résumé en anglais

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 anti-tumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantification 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 co-localized in keratin tumor niches.