4.8 Article

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

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FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.612547

关键词

Nocardia rubra cell wall skeleton; high-risk human papillomavirus; cervical intraepithelial neoplasia; CD4(+) T cell; CD8(+) T cell; programmed cell death-1; programmed cell death-ligand 1

资金

  1. Technology Development Agreement of Hebei Medical University
  2. Weihai Greatest Pharmaceutical Research Institute Co., Ltd., RP China
  3. Nature Science Foundation of Hebei Province [H2017206078]

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The study found that Nr-CWS significantly increased the number of CD4(+) and CD8(+) T cells, reduced the expression of PD-L1 in the patients' local cervical tissues, and decreased the inhibitory effect of the PD-1/PD-L1 pathway. Furthermore, Nr-CWS also promoted immune cell increase and pro-inflammatory cytokine release by upregulating T cell subsets and inhibiting the PD-1/PD-L1 pathway.
The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and after local application of Nr-CWS respectively. The normal control specimens were tested simultaneously. Serial section analysis of immunohistochemistry and co-expression analysis were performed to characterize populations of T cells and the expressions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1). The levels of cytokines in local cervical tissue were also detected. Nr-CWS significantly increased T cells including CD4(+), CD8(+) T cells, and reduced the expression of PD-L1 in the patients' local cervical tissues. Co-expression analyses showed that the proportions of PD-1(+)CD4(+) cells in CD4(+) T cells and PD-1(+)CD8(+) cells in CD8(+) T cells decreased after Nr-CWS application. Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.

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