Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma
Résumé
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 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 colocalized in keratin tumor niches.
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