Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; College of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA.
Biochim Biophys Acta Mol Basis Dis. 2024 Oct;1870(7):167345. doi: 10.1016/j.bbadis.2024.167345. Epub 2024 Jul 9.
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.
头颈部鳞状细胞癌（HNSCC）是全球范围内一个重大的公共卫生关注点。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。巨噬细胞移动抑制因子（MIF）是一种促炎细胞因子，与许多癌症的预后不良有关，但 MIF 在 HNSCC 中的作用机制尚不清楚。我们使用 Mif 或 Mif 小鼠的鼠原位口腔癌模型，确定了宿主来源的 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 Mif 小鼠的肿瘤生长和肿瘤负担较其野生型对照明显降低。对原发性肿瘤部位免疫群体的流式细胞术分析显示，Th1 和细胞毒性 T 细胞向 HNSCC 肿瘤微环境的募集增加。在 Mif 小鼠的肿瘤中，MIF 缺失还增强了抗肿瘤效应 CD8 T 细胞以及 Th1 细胞的效应功能，并减少了肿瘤微环境中粒细胞髓源抑制细胞（g-MDSC）的积累。此外，从荷瘤小鼠中分离的 MDSC 以剂量依赖的方式对 MIF 趋化。综上所述，我们的结果表明宿主来源的 MIF 在促进 HNSCC 中具有趋化和免疫调节作用，并表明针对 MIF 的免疫调节是治疗 HNSCC 的一种有前途的方法。
