IFNγ and TNFα Synergistically Promote Galectin 9 Secretion by Human Osteosarcoma Cells MG-63 to Prevent T Cell Killing

Objectives: Osteosarcoma is the most common bone tumor usually distributed in adolescence and the elderly. IFNγ and TNFα play double-sided roles in tumor immunity. The fundamental mechanism of IFNγ and TNFα in osteosarcoma remains elusive. We speculated that TNFα and IFNγ serve a role in regulating immune checkpoint molecule, Galectin 9, expression of MG-63 osteosarcoma cells.

Methods: The human osteosarcoma cell line, MG-63, was stimulated with recombinant human IFNγ and TNFα. Cytokine stimulated MG-63 cells were cocultured with human peripheral T cells. Real-time PCR, flow cytometry and ELISA were used to detect related molecule expression.

Results: IFNγ and TNFα up-regulate Galectin 9 expression of MG-63 cells synergistically. IFNγ and TNFα stimulated MG-63 cells induce CD4 and CD8 T cell apoptosis and inhibit cytokine production through the Tim-3/Galectin 9 pathway. A High level of serum Galectin 9 and highly expressed Tim-3 of peripheral T cells were detected in osteosarcoma patients.

Conclusion: We found that Galectin-9 is induced by IFNγ and TNFα stimuli in osteosarcoma cells. Furthermore, Tim-3/Galectin-9 pathway contributes to the inducible immunomodulatory functions of osteosarcoma cells, which may provide a new clue to novel strategies for the osteosarcoma therapy.