Zeng Shujie, Zhang Zihao, Ye Chunshui, Wang Jinshen, Jing Changqing, Li Leping
Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Front Oncol. 2023 May 23;13:1171926. doi: 10.3389/fonc.2023.1171926. eCollection 2023.
Semaphorin 4D (SEMA4D) is considered a new antitumor target closely related to immune cells. However, understanding the role of SEMA4D in the tumor microenvironment (TME) is limited. In this study, we explored the expression and immune cell infiltration patterns of SEMA4D using multiple bioinformatics datasets and analyzed the relationship between SEMA4D expression with immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI) and immune function. We detected that SEMA4D is overexpressed in many tumors types, widely enriched in immune cells, and closely associated with TILs, MSI, TMB, as well as T-cell exhaustion-associated immune checkpoints, and thus can broadly affect the immune microenvironment. We further verified the overexpression of SEMA4D in tumor and its distribution in TME by immunohistochemistry, RT-qPCR and flow cytometry, and confirmed that decreased expression of SEMA4D can lead to recovery of T cell exhaustion. In conlusion, this study provides a more comprehensive perspective of SEMA4D regulation of tumor immunity, which provide a new option for cancer immunotherapy.
信号素4D（SEMA4D）被认为是一种与免疫细胞密切相关的新型抗肿瘤靶点。然而，对SEMA4D在肿瘤微环境（TME）中的作用了解有限。在本研究中，我们使用多个生物信息学数据集探索了SEMA4D的表达和免疫细胞浸润模式，并分析了SEMA4D表达与免疫检查点、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和免疫功能之间的关系。我们检测到SEMA4D在多种肿瘤类型中过表达，在免疫细胞中广泛富集，并且与肿瘤浸润淋巴细胞（TILs）、MSI、TMB以及与T细胞耗竭相关的免疫检查点密切相关，因此可广泛影响免疫微环境。我们通过免疫组织化学、RT-qPCR和流式细胞术进一步验证了SEMA4D在肿瘤中的过表达及其在TME中的分布，并证实SEMA4D表达降低可导致T细胞耗竭的恢复。总之，本研究为SEMA4D对肿瘤免疫的调节提供了更全面的视角，为癌症免疫治疗提供了新的选择。
