由于风险管理和治疗策略不理想，头颈鳞状细胞癌 (HNSCC) 患者的预后往往较差；然而，将新型预后生物标志物整合到临床实践中具有挑战性。在这里，我们报告了 HNSCC 患者肿瘤中存在多核巨细胞 (MGC)（一种巨噬细胞），这与未接受治疗和术前接受化疗的患者的良好预后相关。重要的是，术前治疗后肿瘤中 MGC 密度增加，表明这些细胞在抗肿瘤反应中发挥作用。为了将 MGC 密度作为预后标志物进行临床转化，我们开发了一种深度学习模型，可自动对常规染色的病理性全切片图像进行量化。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，并观察到中央记忆 CD4 T 细胞的增加。我们定义了一种 MGC 特异性特征，类似于表达 TREM2 的单核肿瘤相关巨噬细胞，其共定位于角蛋白肿瘤微环境中。

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.