Abstract
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.