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Labelled-free proteomics analysis revealed that the immunosuppressive function of LOXL4 on macrophages primarily relied on IFN-mediated STATs-dependent PD-L1 activation. Hydrogen peroxide scavenge or copper chelation on macrophages abolished the IFN-mediated PD-L1 presentation by LOXL4. In human HCC tissue, expression of LOXL4 in CD68 cells were positively correlated with that of PD-L1 level. High expression of LOXL4 in CD68 cells and low expression of CD8A in tumor tissue cooperatively predict poor survival of HCC patients. LOXL4 facili