title: PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma.
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.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Momoko
authors.initials: M
authors.lastname: Nishikori
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitawaki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sakai
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Hishizawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Tashima
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Kondo
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ohmori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurata
authors.forename: Takamasa
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor