Tim-3 as a diagnostic and prognostic biomarker of osteosarcoma

Abstract

Osteosarcoma is the most frequent primary bone tumor that affects adolescents and children. However, diagnostic and prognostic biomarkers for osteosarcoma remain lacking. (Tim-3) T-cell immunoglobulin domain and mucin domain-3, which negatively regulates T cell helper (Th1) cells and affects cytokine expression, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In this study, we evaluated serum soluble Tim-3 level in osteosarcoma patients to explore its diagnostic and prognostic value for this particular malignancy. Serum soluble Tim-3 level was measured with enzyme-linked immunosorbent assay in 120 osteosarcoma patients, 120 benign bone tumors patients and 120 healthy controls, followed by analysis of the correlation with clinic pathological characteristics. Receiver operating curves, Kaplan-Meier curves, and log-rank analyses as well as Cox proportional hazard models were used to evaluate the diagnostic and prognostic significance. Serum solubleTim-3 level was remarkably elevated in osteosarcoma patients. Osteosarcoma patients with larger tumor size, late stages and distant metastases were accompanied with higher levels of Tim-3. ROC/AUC analysis indicated thatTim-3 served as a reliable marker to distinguish healthy participants from Tim-3 patients. Osteosarcoma patients with higher Tim-3 had relatively lower survival. Multivariate analyses for overall survival revealed that high serum soluble Tim-3 level was an independent prognostic factor for osteosarcoma. Furthermore, Tim-3 levels of CD8+ and CD4+ T cells were elevated in peripheral circulation of osteosarcoma patients. Therefore, It was indicated in our research that elevated serum soluble Tim-3 level might be a novel potential diagnostic and prognostic biomarker for osteosarcoma patients.

TIM3 comes of age as an inhibitory receptor

“…Instead, it has been proposed that soluble TIM3 is a result of metalloproteinase-dependent cleavage that facilitates its shedding from the cell surface 19 . Since elevated plasma levels of TIM3 have been reported in patients with graft-versus-host disease 20 and in patients with osteosarcoma 21 , soluble TIM3 may serve as a biomarker for these maladies. Elevated plasma levels of TIM3 also appear to correlate with enhanced viral load in patients with HIV infection 18 .…”

Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity

“…These soluble-CRs can act as agonists or antagonistic molecular decoys and can orchestrate host immunity distally, performing paracrine tasks similar to stimulatory or inhibitory cytokines. Systemic concentrations of several soluble-CRs rise during inflammation, autoimmunity (Jung et al, 2003;Lahat et al, 2003;Ip et al, 2005Ip et al, , 2006Cao et al, 2012;Delmastro et al, 2012;Chiba et al, 2017;Lin et al, 2018), infectious diseases (Cao et al, 2011;Clayton et al, 2015;Ren et al, 2015;Zilber et al, 2019), and cancer (Prigent et al, 1999;Triebel et al, 2006;Hock et al, 2009;Heo et al, 2012;Ge et al, 2017;Silva et al, 2017;He et al, 2018;Li N. et al, 2018) often mirroring immune dysfunction, disease progression and increased mortality. Measurements of systemic soluble-CRs are useful both as potential diagnostic/prognostic biomarkers (Chen et al, 2017;Li Y. M. et al, 2018) but also to expose mechanisms underlying immunopathogenesis of disease.…”

Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma

“…Upregulation of TIM-3 expression has been observed on exhausted CD8 + T cells (39,40). In certain tumors, such as lung cancer, lymphomas and breast cancer, higher quantities of Tim-3 + CD8 + T cells were associated with poor disease outcomes (41)(42)(43)(44)(45). Ge et al (42) reported that Tim-3 + CD4 + T and CD8 + T cells may serve as novel diagnostic and prognostic biomarkers of OS.…”

“…In certain tumors, such as lung cancer, lymphomas and breast cancer, higher quantities of Tim-3 + CD8 + T cells were associated with poor disease outcomes (41)(42)(43)(44)(45). Ge et al (42) reported that Tim-3 + CD4 + T and CD8 + T cells may serve as novel diagnostic and prognostic biomarkers of OS. However, to the best of our knowledge, the number of Tim-3 + CD8 + T cells in peripheral blood specimens from patients with STS has not been previously investigated, with respect to disease progression and patient survival.…”