Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Yuanyuan Liu; Jingwei Zhang; Zeyu Wang; Xun Zhang; Ziyu Dai; Wantao Wu; Nan Zhang; Zaoqu Liu; Jian Zhang; Peng Luo; Zhipeng Wen; Jing Yu; Hao Zhang; Tubao Yang; Quan Cheng

doi:10.3389/fcell.2022.821649

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Front Cell Dev Biol. 2022 Apr 12:10:821649. doi: 10.3389/fcell.2022.821649. eCollection 2022.

Authors

Yuanyuan Liu^{1

2}, Jingwei Zhang^{2

3}, Zeyu Wang^{2

3}, Xun Zhang^{2

3}, Ziyu Dai^{2

3}, Wantao Wu^{2

4}, Nan Zhang⁵, Zaoqu Liu⁶, Jian Zhang⁷, Peng Luo⁷, Zhipeng Wen⁸, Jing Yu⁹, Hao Zhang^{2

3}, Tubao Yang^{1

2}, Quan Cheng^{2

3

10}

Affiliations

¹ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Changsha, China.
³ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
⁵ One-third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
⁶ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁷ Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
⁸ Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
⁹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
¹⁰ Clinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, Changsha, China.

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.

Keywords: VSIR; immunotherapy; macrophages; t cells; tumor microenvironment.