PD-1–PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma

Programmed death-1 (PD-1)-PD-1 ligand (PD-L) signaling system is involved in the functional impairment of T cells such as in chronic viral infection or tumor immune evasion. We examined PD-L expression in lymphoid cell lines and found that they were up-regulated on Hodgkin lymphoma (HL) and several T-cell lymphomas but not on B-cell lymphomas. PD-L expression was also demonstrated in primary Hodgkin/Reed-Sternberg (H/RS) cells. On the other hand, PD-1 was elevated markedly in tumor-infiltrating T cells of HL, and was high in the peripheral T cells of HL patients as well. Blockade of the PD-1 signaling pathway inhibited SHP-2 phosphorylation and restored the IFN-gamma-producing function of HL-infiltrating T cells. According to these results, deficient cellular immunity observed in HL patients can be explained by "T-cell exhaustion," which is led by the activation of PD-1-PD-L signaling pathway. Our finding provides a potentially effective immunologic strategy for the treatment of HL.