T 细胞激活的 V 域 Ig 抑制因子 (VISTA) 是一种新型免疫检查点调节剂，可以抑制 T 细胞介导的抗肿瘤免疫。尽管抗VISTA单克隆抗体的使用在各种恶性肿瘤的治疗中显示出令人鼓舞的结果，但其对口腔鳞状细胞癌（OSCC）的具体影响和潜在机制仍有待探索。在这项工作中，我们分析了人 OSCC 组织微阵列、人外周血单核细胞和免疫活性转基因小鼠模型，以研究 VISTA 高表达与骨髓源性免疫抑制细胞（MDSC；CD11b、CD33、Arginase-1）标记物之间的关系，肿瘤相关巨噬细胞（CD68、CD163、CD206）和 T 细胞功能（CD8、PD-L1、颗粒酶 B）。在OSCC中，我们发现VISTA在MDSC中高表达且稳定表达。此外，我们建立了小鼠 OSCC 原位异种移植肿瘤模型，以研究 VISTA 阻断对肿瘤微环境的影响。我们发现 VISTA 阻断可减少免疫抑制微环境并延缓肿瘤生长。这是通过抑制 MDSC 的数量和功能，同时增强肿瘤浸润 T 细胞的功能来实现的。我们的研究表明，MDSC 表达的 VISTA 在 OSCC 的进展中具有至关重要的功能，VISTA 阻断疗法是一种有前途的免疫检查点阻断疗法。版权所有 © 2023 Elsevier B.V. 保留所有权利。

V-domain Ig suppressor of T-cell activation (VISTA) is a novel immune checkpoint regulator that can inhibit T cell-mediated antitumor immunity. Although the use of anti-VISTA monoclonal antibody has demonstrated encouraging outcomes in the therapy of various malignancies, its specific impact and underlying mechanisms in oral squamous cell carcinoma (OSCC) remain to be explored. In this work, we analyzed human OSCC tissue microarrays, human peripheral blood mononuclear cells, and immunocompetent transgenic mouse models to investigate the relationship between high VISTA expression and markers of myeloid-derived immunosuppressive cells (MDSCs; CD11b, CD33, Arginase-1), tumor-associated macrophages (CD68, CD163, CD206), and T cell function (CD8, PD-L1, Granzyme B). In OSCC, we discovered that VISTA was highly expressed and stably expressed in MDSCs. Furthermore, we established a mouse OSCC orthotopic xenograft tumor model to investigate the impact of VISTA blockade on the tumor microenvironment. We found that VISTA blockade reduces the immunosuppressive microenvironment and delays tumor growth. This is achieved by suppressing the quantity and function of MDSCs while boosting the function of tumor-infiltrating T cells. Our research indicated that VISTA expressed by MDSCs has a crucial function in the progression of OSCC and that VISTA blockade therapy is a promising immune checkpoint blockade therapy.Copyright © 2023 Elsevier B.V. All rights reserved.