TIM‑3 expression and its association with overall survival in primary osteosarcoma

Abstract

T-cell immunoglobulin and mucin domaincontaining-3 (TIM-3) performs a critical function in immune tolerance by suppressing the activation and proliferation of T cells. TIM-3 serves an important role in tumor progression in a number of carcinomas, including non-small cell lung cancer, hepatitis B virus-associated hepatocellular carcinoma, Langerhans cell sarcoma, head and neck cancer and follicular B cell non-Hodgkin lymphoma. The aim of the present study was to evaluate the possible association of TIM-3 with the prognosis of osteosarcoma. TIM-3 expression was assessed by immunohistochemical analysis in osteosarcoma tissues. The association between TIM-3 expression and prognosis was examined. To assess the association between TIM-3 expression levels and clinicopathological features, a Fisher's exact test was used. TIM-3 overexpression was indicated to be associated with surgical treatment and survival. Kaplan-Meier analysis indicated that TIM-3 is an independent predictor of overall survival, and its overexpression was indicated to be associated with poor prognosis in patients with osteosarcoma. Additionally, reverse transcription-quantitative polymerase chain reaction and western blot analysis were carried out to evaluate TIM-3 expression levels in fresh tumor tissue samples, adjacent-tissue samples, osteosarcoma cell lines, and in an osteoblastic cell line. TIM-3 was indicated to be overexpressed in fresh osteosarcoma tissue samples and in osteosarcoma cell lines. In conclusion, TIM-3 overexpression is associated with poor survival among patients with osteosarcoma and may be a possible therapeutic target in these types of tumors.

Prognostic Values of TIM-3 Expression in Patients With Solid Tumors: A Meta-Analysis and Database Evaluation

“…A total of 3,072 patients, ranging from 30 to 587 patients per study, were involved in our meta-analysis. Among all eligible studies, 13 studies focused on the TIM-3 expression on tumor cells ( 10 – 14 , 28 – 33 , 36 , 39 ), six studies centered on the TIM-3 expression on TILs ( 9 , 34 , 35 , 37 , 38 , 40 ), one study combined the TIM-3 expression on tumor cells and TILs ( 41 ), and one study analyzed the TIM-3 expression on tumor cells and TILs separately ( 42 ). All researches utilized the IHC techniques to detect the expression level of TIM-3.…”

Tumor-derived Exosomes Induced M2 Macrophage Polarization and Promoted the Metastasis of Osteosarcoma Cells Through Tim-3

“…Tim-3 by binding to its ligand Galectin-9 (Gal-9) could induce apoptosis and immune tolerance of T cells. In this study, Tim-3 was also found to be expressed in macrophages, NK cells, and other natural immune cells, which may play an important role in maintaining immune homeostasis [30]. Using Western blot assay, we detected high expression of Tim-3 protein in osteosarcoma tissues and cells., which was consistent with previous studies.…”

“…Tim-3 could induce macrophage M2 differentiation and aggravate podocyte damage to participate in the occurrence and development of the disease through NF-κB/TNF-α pathway in diabetic nephropathy [28,29]. In osteosarcoma, it has been documented that the expression of Tim-3 is signi cantly increased in tumor tissue [30], and the overexpression of Tim-3 could promote the occurrence and development of osteosarcoma. However, whether the overexpression of Tim-3 in osteosarcoma could also regulate the differentiation of tumor-associated macrophages and the underlying molecular mechanism of this regulation remains elusive.…”

Prospects for NK Cell Therapy of Sarcoma

“…Knockout of IL-1R8 has been shown to restore NK cell antitumor function in MCA-induced sarcomas, implicating a role of IL-1R8 in sarcoma-mediated NK cell suppression [ 92 ]. Expression of other checkpoint molecules such as T-cell immunoglobulin and mucin domain-3 (TIM-3) ligands and NKp44-inhibiting proliferating cell nuclear antigen (PCNA) was also reported in sarcomas [ 45 , 139 ].…”