Abstract
Regulatory T cells (Tregs) are immunosuppressive T cells that play an important role in immune homeostasis. Multiple markers have been associated with the characterization, as well as function of Tregs. Recently, glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine-rich repeats, has been found to be highly expressed on the surface of activated Tregs. GARP maintains Tregs’ regulatory function and homeostasis through the activation and secretion of transforming growth factor β. In this study, we investigated the expression of GARP in Tregs from the peripheral blood (PB) and tumor tissues of lung cancer patients. The association between the proportion and expression level of GARP on Tregs and the clinicopathological factors of lung cancer patients was also analyzed. Results showed that in the tumor tissues of patients with lung cancer, GARP expression was increased in Tregs and was associated with lymph node metastasis, distant metastasis, and clinical stage. Furthermore, the infiltrating Tregs from early stage patients exhibited higher GARP expression than that from advanced cancer patients, which indicated that GARP might be an early prognostic biomarker. In vitro coculture studies demonstrated that human lung cancer cell lines might induce the expression of GARP in Tregs by certain mechanisms. Overall, this research demonstrated the potential value of GARP in Tregs definition and cancer immunotherapy.
Highlights
Accumulating evidence has indicated that tumor microenvironment plays an important role in tumor progression, invasion, and metastasis [1]
Many molecules contribute to the immunosuppressive function of Tregs, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), tumor necrosis factor receptor 2, lymphocyte activation gene 3, T cell membrane protein 3, and glycoprotein A repetitions predominant (GARP) [26,27,28,29]
One sure thing was that GARP+ Tregs possessed high immune suppression, and GARP–transforming growth factor β (TGF-β) pathway is the major way of suppressive function in this subset
Summary
Accumulating evidence has indicated that tumor microenvironment plays an important role in tumor progression, invasion, and metastasis [1]. Tumors possess infiltrating cells of both innate and acquired immunity, such as myeloidderived suppressor cells, macrophages, dendritic cells, mast cells, eosinophils, neutrophils, NK cells, and lymphocytes. These cells coordinately form a complex regulatory network, which fosters tumor growth by creating an environment that enables cancer to evade immune surveillance and destruction [3]. A number of studies have provided clear evidence that the number of tumor-infiltrating Tregs was increased in multiple tumors, such as renal carcinoma, gastrointestinal cancer, breast carcinoma, lung cancer, prostatic carcinoma, melanoma, and ovarian carcinoma [4,5,6,7,8,9,10]
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