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Increased expression of programmed death (PD)‐1 and its ligand PD ‐L1 correlates with impaired cell‐mediated immunity in high‐risk human papillomavirus‐related cervical intraepithelial neoplasia
Author(s) -
Yang Wen,
Song Yan,
Lu YunLong,
Sun JunZhong,
Wang HongWei
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12101
Subject(s) - human papillomavirus , cervical intraepithelial neoplasia , immunity , ligand (biochemistry) , immunology , medicine , immune system , cancer research , cervical cancer , receptor , cancer
Summary Impaired local cellular immunity contributes to the pathogenesis of persistent high‐risk human papillomavirus ( HR ‐ HPV ) infection and related cervical intraepithelial neoplasia ( CIN ), but the underlying molecular mechanisms remain unclear. Recently, the programmed death 1/programmed death 1 ligand ( PD ‐1/ PD ‐ L 1; CD 279/ CD 274) pathway was demonstrated to play a critical role in attenuating T ‐cell responses and promoting T ‐cell tolerance during chronic viral infections. In this study, we examined the expression of PD ‐1 and PD ‐ L 1 on cervical T cells and dendritic cells ( DC s), respectively, from 40 women who were HR ‐ HPV ‐negative (−) or HR ‐ HPV ‐positive (+) with CIN grades 0, I and II – III . We also measured interferon‐γ, interleukin‐12 ( IL ‐12) and IL ‐10 in cervical exudates. The most common HPV type was HPV 16, followed by HPV 18, 33, 51 and 58. PD ‐1 and PD ‐ L 1 expression on cervical T cells and DC s, respectively, was associated with HR ‐ HPV positivity and increased in parallel with increasing CIN grade. The opposite pattern was observed for CD 80 and CD 86 expression on DC s, which decreased in HR ‐ HPV (+) patients in parallel with increasing CIN grade. Similarly, reduced levels of the T helper type 1 cytokines interferon‐γ and IL ‐12 and increased levels of the T helper type 2 cytokine IL ‐10 in cervical exudates correlated with HR ‐ HPV positivity and CIN grade. Our results suggest that up‐regulation of the inhibitory PD ‐1/ PD ‐L1 pathway may negatively regulate cervical cell‐mediated immunity to HPV and contribute to the progression of HR ‐ HPV ‐related CIN . These results may aid in the development of PD ‐1/ PD ‐ L 1 pathway‐based strategies for immunotherapy of HR ‐ HPV ‐related CIN .