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

R Yamamoto, M Nishikori, T Kitawaki… - Blood, The Journal …, 2008 - ashpublications.org
R Yamamoto, M Nishikori, T Kitawaki, T Sakai, M Hishizawa, M Tashima, T Kondo, K Ohmori…
Blood, The Journal of the American Society of Hematology, 2008ashpublications.org
Abstract 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 …
Abstract
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-γ–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.
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