头颈鳞状细胞癌（HNSCC）是全球重大的公共卫生问题。 HNSCC 肿瘤微环境中的免疫调节靶点对于增强 HNSCC 免疫治疗的疗效至关重要。巨噬细胞迁移抑制因子 (MIF) 是一种促炎细胞因子，与许多癌症的不良预后有关，但 MIF 在 HNSCC 中的机制作用仍不清楚。使用 Mif / 或 Mif-/- 小鼠的鼠原位口腔癌模型，我们确定了宿主衍生的 MIF 在 HNSCC 肿瘤发展、转移以及局部和全身肿瘤免疫反应中的功能。我们观察到，与野生型小鼠相比，Mif-/- 小鼠的肿瘤生长和肿瘤负荷减少。对原发肿瘤位点内免疫群体的流式细胞术分析显示，HNSCC 肿瘤微环境中 Th1 和细胞毒性 T 细胞的招募增加。在 Mif-/- 小鼠的肿瘤内，MIF 缺失还增强了抗肿瘤效应 CD8 T 细胞和 Th1 细胞的效应功能，并减少了肿瘤微环境中粒细胞骨髓源性抑制细胞 (g-MDSC) 的积累。此外，从荷瘤小鼠中分离出的 MDSC 以剂量依赖性方式对 MIF 产生趋化反应。总而言之，我们的结果证明了宿主衍生的 MIF 在促进 HNSCC 方面具有趋化和免疫调节作用，并表明 MIF 靶向免疫调节是 HNSCC 治疗的一种有前景的方法。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Head and neck squamous cell carcinoma (HNSCC) is a significant public health concern worldwide. Immunomodulatory targets in the HNSCC tumor microenvironment are crucial to enhance the efficacy of HNSCC immunotherapy. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that has been linked to poor prognosis in many cancers, but the mechanistic role of MIF in HNSCC remains unclear. Using a murine orthotopic oral cancer model in Mif+/+ or Mif-/- mice, we determined the function of host derived MIF in HNSCC tumor development, metastasis as well as localized and systemic tumor immune responses. We observed that Mif-/- mice have decreased tumor growth and tumor burden compared to their wild-type counterparts. Flow cytometric analysis of immune populations within the primary tumor site revealed increased Th1 and cytotoxic T cell recruitment to the HNSCC tumor microenvironment. Within the tumors of Mif-/- mice, MIF deletion also enhanced the effector function of anti-tumoral effector CD8+ T cells as well as Th1 cells and decreased the accumulation of granulocytic myeloid derived suppressor cells (g-MDSCs) in the tumor microenvironment. Furthermore, MDSCs isolated from tumor bearing mice chemotactically respond to MIF in a dose dependent manner. Taken together, our results demonstrate a chemotactic and immunomodulatory role for host derived MIF in promoting HNSCC and suggest that MIF targeted immunomodulation is a promising approach for HNSCC treatment.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.