Based on the finding that PD-L1 is up-regulated on HL cells, and PD-1 is markedly elevated in the tumor-infiltrating or peripheral T cells of HL patients, blockade of the PD-1 signaling pathway inhibits SHP-2 phosphorylation and restores the IFN-γ-producing function of HL-infiltrating T-cells [44]. This evidence concerns the gene CD274 and Hodgkins lymphoma.