本研究旨在揭示头颈鳞状细胞癌 (HNSCC) 中 M2 巨噬细胞极化的机制，并确定潜在的治疗靶点。我们利用 TCGA 和 GEO 数据库中的 HNSCC 大量转录组进行了综合生物信息学分析，以查明影响 M2 巨噬细胞的关键因素极化和肿瘤预后。这些基因的重要性在功能分析、单细胞转录组数据集和体外实验中得到了验证。通过基因敲除、细胞共培养和其他定量分析，进一步探讨了它们调节 M2 巨噬细胞极化的机制。我们鉴定了与 M2 巨噬细胞浸润相关的 5 个基因的新预后特征，其中 SCG2 成为 M2 巨噬细胞极化的关键因素在 HNSCC。肿瘤患者中 SCG2 的高表达与较差的预后相关，敲除 SCG2 会减少 HNSCC 细胞的增殖和迁移，从而破坏 M2 巨噬细胞极化。此外，干扰SCG2会导致CCL2和TGFβ1等促肿瘤细胞因子的分泌显着减少。我们的研究结果为HNSCC的发病机制提供了更深入的见解，并为HNSCC，特别是SCG2，抑制M2巨噬细胞极化提供了有希望的治疗靶点并调节细胞因子分泌。© 2024 John Wiley

This study aims to unravel the mechanisms underlying M2 macrophage polarization in head and neck squamous cell carcinoma (HNSCC), and identify potential therapeutic targets.We conducted an integrated bioinformatic analysis using HNSCC bulk transcriptomes from TCGA and GEO databases to pinpoint critical factors influencing M2 macrophage polarization and tumor prognosis. The significance of these genes was validated in function analysis, single-cell transcriptome datasets, and in vitro experiments. Their mechanisms in modulating M2 macrophage polarization were further explored by gene knockdown, cell coculture, and other assays for quantification.We identified a novel prognostic signature of five genes associated with M2 macrophage infiltration, in which SCG2 emerged as a pivotal factor in M2 macrophage polarization in HNSCC. High expression of SCG2 in tumor patients correlated with poorer prognoses, and knocking down SCG2 reduced the proliferation and migration of HNSCC cells, disrupting M2 macrophage polarization. Furthermore, interference of SCG2 resulted in a significant decrease in the secretion of pro-tumor cytokines such as CCL2 and TGFβ1.Our findings provide deeper insights into the pathogenesis of HNSCC and offer promising therapeutic targets for HNSCC, especially SCG2, to inhibit M2 macrophage polarization and modulate cytokine secretion.© 2024 John Wiley & Sons Ltd.