Abnormal expression of Tim-3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients

Abstract

T-cell immunoglobulin and mucin-domain-3-containing molecule 3 (TIM-3) plays a pivotal role in immune regulation and has been found in various tumors. However, the prevalence and distribution of Tim-3 in osteosarcoma (OS) is still unclear. The aim of this study was to investigate the prevalence and distribution of Tim-3 in OS. Tim-3 on peripheral T cells from 82 OS patients and 60 healthy controls were examined by flow cytometry. Plasma levels of IL-2, IFN-γ, and TNF-α were measured by ELSIA. Tim-3 on both CD4+ T and CD8+ T cells were significantly upregulated in OS patients compared with healthy controls, Tim-3+ CD4+ T, and Tim-3+ CD8+ T cells were both negatively associated with serum levels of IL-2 and IFN-γ and TNF-α. In addition, Tim-3 showed similar levels in patients with different tumor sites. Nevertheless, patients with advanced tumor stage, metastasis, and pathological tumor fracture displayed significantly higher Tim-3 on both CD4+ T cells and CD8+ T cells than those with early tumor stage, without metastasis and pathological tumor fracture. Moreover, high Tim-3 on peripheral CD4+ T cells or CD8+ T were significantly related to poor overall survival (P = 0.014, P = 0.035, respectively). In conclusion, Tim-3 may be a potential diagnostic and prognostic biomarker for OS progression.