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

Blood. 2008 Mar 15;111(6):3220-4. doi: 10.1182/blood-2007-05-085159. Epub 2008 Jan 18.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • B7-H1 Antigen
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hodgkin Disease / genetics
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor
  • Protein Binding
  • Signal Transduction

Substances

  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor