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.

中文翻译：

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表达 Trem2 的多核巨噬细胞是头颈部鳞状细胞癌预后良好的生物标志物


头颈部鳞状细胞癌 （HNSCC） 患者由于风险管理和治疗策略不理想，通常预后不佳;然而，将新的预后生物标志物整合到临床实践中具有挑战性。在这里，我们报道了 HNSCC 患者肿瘤中存在多核巨细胞 （MGC） – 一种巨噬细胞 – 这与初治和术前化疗患者的良好预后相关。重要的是，术前治疗后肿瘤中的 MGC 密度增加，表明这些细胞在抗肿瘤反应中的作用。为了能够将 MGC 密度临床转化为预后标志物，我们开发了一个深度学习模型，以自动量化常规染色的病理全玻片图像。最后，我们使用空间转录组学和蛋白质组学方法来描述 MGC 相关的肿瘤微环境，并观察到中枢记忆 CD4 T 细胞的增加。我们定义了一个 MGC 特异性特征，类似于表达 TREM2 的单核肿瘤相关巨噬细胞，它们共定位于角蛋白肿瘤生态位中。