MIF and cancer: In co-culture experiments, SIGLEC15 was found to be highly expressed in ATC cells expressing the cancer stem cell marker CD44, SIGLEC15high cancer cells not only express predominantly interact with T cells through immunosuppressive signals such as MIF-TNFRSF14 and CXCL12-CXCR4 to promote immunosuppression, but also reduce the production of anti-tumor cytokines IFN-γ and IL-2 by down-regulating the NF-κB/NFAT pathway, creating an immunosuppressive microenvironment conducive to tumor development (124).