SPP1 and osteosarcoma: It has been found that interferon regulatory factor 8 associates with osteopontin and causes a downregulation of osteopontin levels, which then activates T cells, meaning that interferon regulatory factor 8 levels are negatively correlated with osteopontin levels and that a decrease in interferon regulatory factor 8 levels leads to an upregulation of osteopontin levels, which can then reduce or even block the activation of T cells, which ultimately leads to immune escape from cancer, including osteosarcoma (101).