Functional modulation of CD8+ T cell by approved novel immune enhancer: Nocardia rubra Cell-Wall Skeletons (Nr-CWS)

Tao, Yicheng; Wang, Guangchuan; Zhai, Jingbo; Zhang, Ning

doi:10.1016/j.intimp.2019.106023

Cited by 9 publications

(19 citation statements)

References 26 publications

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“…The possible mechanism involves Nr‐CWS reducing the expression levels of PD‐L1 and attenuating the immunosuppression. Based on these results, we hypothesize that Nr‐CWS enhances the antitumor effect of dendritic cells and macrophages 15,16 …”

Section: Discussionmentioning

confidence: 86%

“…Nr‐CWS can significantly promote the activity of Cytokine‐Induced Killer cells, DCs and Natural Killer cells, which exert strong antitumor activity especially by inducing apoptosis 14 . In addition, Nr‐CWS increases the response of CD8+T cell and activation of CD4+T cell, and promotes the differentiation of CD4+T cells into Th1 cells 15,16 . Ct26.WT tumor‐bearing mice were injected with Nr‐CWS and PD‐1 inhibitors simultaneously, which significantly inhibited the growth of transplanted tumor.…”

Section: Introductionmentioning

confidence: 99%

“… 14 In addition, Nr‐CWS increases the response of CD8+T cell and activation of CD4+T cell, and promotes the differentiation of CD4+T cells into Th1 cells. 15 , 16 Ct26.WT tumor‐bearing mice were injected with Nr‐CWS and PD‐1 inhibitors simultaneously, which significantly inhibited the growth of transplanted tumor. This suggests that Nr‐CWS may improve the efficacy of PD‐1 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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Background As an immune enhancer, Nocardia rubra cell‐wall skeleton (Nr‐CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. Methods In our study, the aim was to determine whether Nr‐CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. Results The experimental results showed that Nr‐CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL‐6, IL‐12, TNF‐ɑ, and IL‐1β secreted by dendritic cells and macrophages and reduced their PD‐L1 expression. In vitro, Nr‐CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr‐CWS promoted TNF‐ɑ/TNFR1/caspase‐8‐mediated apoptosis by increasing macrophages secretion of TNF‐ɑ and inhibited cell migration and invasion regulated by the WNT/β‐catenin‐EMT pathway. Nr‐CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD‐L1 gene. In vivo, Nr‐CWS inhibited tumor growth and decreased the expression of E6, E7, PD‐L1, P16, Ki67, and PCNA in tumors. Conclusions Therefore, our results suggest that Nr‐CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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“…Nr-CWS was first reported by Azuma et al in 1976 (9) and was subsequently shown to exert antitumor effects and affect the complex immune network formed by interactions of immunocompetent cells (10). Recently, it has been proved in vitro that Nr-CWS could stimulate macrophages (11), dendritic cells, natural killer cells (12), CD4 + T cells (13), and CD8 + T cells (14), which imply its potential application in immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Zhang²,

Zhao

et al. 2021

Front. Immunol.

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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-γ (IFN-γ), tumor necrosis factor-α (TNF-α), 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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“…There is evidence that N-CWS can activate macrophages and induce killer T cells ( 24 ). N‐CWS can be used as immunostimulatory therapy for DC proliferation and phenotypic and functional maturation ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report

et al. 2022

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Personal neoantigen vaccines are considered to be effective methods for inducing, amplifying and diversifying antitumor T cell responses. We recently conducted a clinical study that combined neoantigen nanovaccine with anti-PD-1 antibody. Here, we reported a case with a clear beneficial outcome from this treatment. We established a process that includes comprehensive identification of individual mutations, computational prediction of new epitopes, and design and manufacture of unique nanovaccines for this patient. Nanovaccine started after a relapse in third-line treatment. We assessed the patient’s clinical outcome and circulating immune response. In this advanced pancreatic cancer patient, the OS associated with the vaccine treatment was 10.5 months. A peptide-specific T-cell response against 9 of the 12 vaccine peptides could be detected sequentially. Robust neoantigen-specific T cell responses were also detected by IFN-γ ELISPOT and intracellular cytokine staining. In conclusion, sustained functional neoantigen-specific T cell therapy combined with immune checkpoint targeting may be well suited to help control progressive metastatic pancreatic cancer.

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Functional modulation of CD8+ T cell by approved novel immune enhancer: Nocardia rubra Cell-Wall Skeletons (Nr-CWS)

Cited by 9 publications

References 26 publications

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

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

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report

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