Liu Yuanyuan, Zhang Jingwei, Wang Zeyu, Zhang Xun, Dai Ziyu, Wu Wantao, Zhang Nan, Liu Zaoqu, Zhang Jian, Luo Peng, Wen Zhipeng, Yu Jing, Zhang Hao, Yang Tubao, Cheng Quan
Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Changsha, China.
Front Cell Dev Biol. 2022 Apr 12;10:821649. doi: 10.3389/fcell.2022.821649. eCollection 2022.
VSIR is a critical immunomodulatory receptor that inhibits T cell effector function and maintains peripheral tolerance. However, the mechanism by which VSIR participates in tumor immunity in the pan-cancer tumor microenvironment remains unclear. This study systematically explored the prognostic and immune profile of VSIR in the tumor microenvironment of 33 cancers. We compared the expression patterns and molecular features of VSIR in the normal and cancer samples both from the public databases and tumor chips. VSIR level was significantly related to patients' prognosis and could be a promising predictor in many tumor types, such as GBM, KIRC, SKCM, READ, and PRAD. Elevated VSIR was closely correlated with infiltrated inflammatory cells, neoantigens expression, MSI, TMB, and classical immune checkpoints in the tumor microenvironment. Enrichment signaling pathways analysis indicated VSIR was involved in several immune-related pathways such as activation, proliferation, and migration of fibroblast, T cell, mast cell, macrophages, and foam cell. In addition, VSIR was found to widely express on cancer cells, fibroblasts, macrophages, and T cells in many tumor types based on the single-cell sequencing analysis and co-express with M2 macrophage markers CD68, CD163 based on the immunofluorescence staining. Finally, we predicted the sensitive drugs targeting VSIR and the immunotherapeutic value of VSIR. In sum, VSIR levels strongly correlated with the clinical outcome and tumor immunity in multiple cancer types. Therefore, therapeutic strategies targeting VSIR in the tumor microenvironment may be valuable tools for cancer immunotherapy.
VSIR是一种关键的免疫调节受体，可抑制T细胞效应功能并维持外周免疫耐受。然而，VSIR在泛癌肿瘤微环境中参与肿瘤免疫的机制仍不清楚。本研究系统地探讨了VSIR在33种癌症肿瘤微环境中的预后和免疫特征。我们比较了来自公共数据库和肿瘤芯片的正常样本和癌症样本中VSIR的表达模式和分子特征。VSIR水平与患者预后显著相关，并且在许多肿瘤类型中，如胶质母细胞瘤（GBM）、肾透明细胞癌（KIRC）、皮肤黑色素瘤（SKCM）、直肠癌（READ）和前列腺癌（PRAD），它可能是一个有前景的预测指标。肿瘤微环境中VSIR水平升高与浸润性炎症细胞、新抗原表达、微卫星高度不稳定（MSI）、肿瘤突变负荷（TMB）以及经典免疫检查点密切相关。富集信号通路分析表明，VSIR参与了多种免疫相关通路，如成纤维细胞、T细胞、肥大细胞、巨噬细胞和泡沫细胞的激活、增殖和迁移。此外，基于单细胞测序分析发现，VSIR在许多肿瘤类型的癌细胞、成纤维细胞、巨噬细胞和T细胞上广泛表达，并且基于免疫荧光染色发现它与M2巨噬细胞标志物CD68、CD163共表达。最后，我们预测了靶向VSIR的敏感药物以及VSIR的免疫治疗价值。总之，VSIR水平与多种癌症类型的临床结局和肿瘤免疫密切相关。因此，在肿瘤微环境中靶向VSIR的治疗策略可能是癌症免疫治疗的有价值工具。
