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The attenuated hepatocellular carcinoma-specific Listeria vaccine Lmdd-MPFG prevents tumor occurrence through immune regulation of dendritic cells.

Wan X, Cheng C, Lin Z, Jiang R, Zhao W, Yan X, Tang J, Yao K, Sun B, Chen Y - Oncotarget (2015)

Bottom Line: Additionally, the Lmdd-MPFG vaccine caused maturation of DCs in vitro.We demonstrated the synergistic effect of TLR4 and NLRP3 or NOD1 signaling pathways in LM-induced DC activation.These results suggest that the Lmdd-MPFG vaccine is a feasible strategy for preventing HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China.

ABSTRACT
Immunotherapy is a promising treatment for liver cancer. Here, we tested the ability of the attenuated hepatocellular carcinoma-specific Listeria vaccine (Lmdd-MPFG) to treat hepatocellular carcinoma (HCC) in a mouse model. Immunization with the vaccine caused a strong anti-tumor response, especially in mice reinfused with dendritic cells (DCs). In mice that were also administered DCs, tumor suppression was accompanied by the strongest cytotoxic T lymphocyte response of all treatment groups and by induced differentiation of CD4+ T cells, especially Th17 cells. Additionally, the Lmdd-MPFG vaccine caused maturation of DCs in vitro. We demonstrated the synergistic effect of TLR4 and NLRP3 or NOD1 signaling pathways in LM-induced DC activation. These results suggest that the Lmdd-MPFG vaccine is a feasible strategy for preventing HCC.

No MeSH data available.


Related in: MedlinePlus

Cross-presentation of NLRs and TLRs in LM-treated DCsDCs were harvested after 24 hours of LM infection (at a MOI of 10) (or of incubation without LM) and then treated to silence or stimulate NLRP3 expression with corresponding receptor agonists (LPS, TLR4 agonist; MDP, NOD1/2 agonist; MSU, NLRP3 agonist) for 6-8 h as described in the Materials and Methods section. Expression of the functional DC molecules CD80 and CD86 was assessed by flow cytometry, and the peak with gray filled represents the control (A and B). Supernatants were collected for quantification of IL-12p70, IL-β, TNF-αand IFN-γ by ELISA (C). Protein levels of NOD1, NLRP3 and TLR4 (D) and expression of NF-kB and caspase-1 (E) were detected by western blot. GAPDH was used as the internal control, and summary statistics are depicted in the histograms. Each data point represents the mean ± SEM from three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).
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Figure 3: Cross-presentation of NLRs and TLRs in LM-treated DCsDCs were harvested after 24 hours of LM infection (at a MOI of 10) (or of incubation without LM) and then treated to silence or stimulate NLRP3 expression with corresponding receptor agonists (LPS, TLR4 agonist; MDP, NOD1/2 agonist; MSU, NLRP3 agonist) for 6-8 h as described in the Materials and Methods section. Expression of the functional DC molecules CD80 and CD86 was assessed by flow cytometry, and the peak with gray filled represents the control (A and B). Supernatants were collected for quantification of IL-12p70, IL-β, TNF-αand IFN-γ by ELISA (C). Protein levels of NOD1, NLRP3 and TLR4 (D) and expression of NF-kB and caspase-1 (E) were detected by western blot. GAPDH was used as the internal control, and summary statistics are depicted in the histograms. Each data point represents the mean ± SEM from three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).

Mentions: To further confirm the effect on NLRP3 expression and the interactions between the NLRP3, NOD1/2 and TLR4 signaling pathways in the LM-induced DC-activation process, we collected immature DCs and subjected them to different treatments (control, MDP, LPS+MSU, MSU, MDP+MSU, SiNLRP3). NLRP3 expression was silenced in immature DCs with or without LM infection. After stimulation by corresponding agonists (LPS, TLR4 agonist; MDP, NOD1/2 agonist; and MSU, NLRP3 agonist) for 6-8 h, DC functional phenotypes were detected by flow cytometry (Fig. 3A and 3B). We found that both the CD80 and CD86 expression levels were down-regulated in SiNLRP3 DCs compared to the control, which indicated an important role for NLRP3 in DC activation. Without LM stimulation, CD80 and CD86 levels were increased in the MSU-treated group, and a higher expression occurred with MSU treatment combined with LPS and MDP. More significant changes were observed in the LM-stimulated groups; the combination of agonists led to significant up-regulation in LM-induced DC maturation.


The attenuated hepatocellular carcinoma-specific Listeria vaccine Lmdd-MPFG prevents tumor occurrence through immune regulation of dendritic cells.

Wan X, Cheng C, Lin Z, Jiang R, Zhao W, Yan X, Tang J, Yao K, Sun B, Chen Y - Oncotarget (2015)

Cross-presentation of NLRs and TLRs in LM-treated DCsDCs were harvested after 24 hours of LM infection (at a MOI of 10) (or of incubation without LM) and then treated to silence or stimulate NLRP3 expression with corresponding receptor agonists (LPS, TLR4 agonist; MDP, NOD1/2 agonist; MSU, NLRP3 agonist) for 6-8 h as described in the Materials and Methods section. Expression of the functional DC molecules CD80 and CD86 was assessed by flow cytometry, and the peak with gray filled represents the control (A and B). Supernatants were collected for quantification of IL-12p70, IL-β, TNF-αand IFN-γ by ELISA (C). Protein levels of NOD1, NLRP3 and TLR4 (D) and expression of NF-kB and caspase-1 (E) were detected by western blot. GAPDH was used as the internal control, and summary statistics are depicted in the histograms. Each data point represents the mean ± SEM from three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496186&req=5

Figure 3: Cross-presentation of NLRs and TLRs in LM-treated DCsDCs were harvested after 24 hours of LM infection (at a MOI of 10) (or of incubation without LM) and then treated to silence or stimulate NLRP3 expression with corresponding receptor agonists (LPS, TLR4 agonist; MDP, NOD1/2 agonist; MSU, NLRP3 agonist) for 6-8 h as described in the Materials and Methods section. Expression of the functional DC molecules CD80 and CD86 was assessed by flow cytometry, and the peak with gray filled represents the control (A and B). Supernatants were collected for quantification of IL-12p70, IL-β, TNF-αand IFN-γ by ELISA (C). Protein levels of NOD1, NLRP3 and TLR4 (D) and expression of NF-kB and caspase-1 (E) were detected by western blot. GAPDH was used as the internal control, and summary statistics are depicted in the histograms. Each data point represents the mean ± SEM from three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).
Mentions: To further confirm the effect on NLRP3 expression and the interactions between the NLRP3, NOD1/2 and TLR4 signaling pathways in the LM-induced DC-activation process, we collected immature DCs and subjected them to different treatments (control, MDP, LPS+MSU, MSU, MDP+MSU, SiNLRP3). NLRP3 expression was silenced in immature DCs with or without LM infection. After stimulation by corresponding agonists (LPS, TLR4 agonist; MDP, NOD1/2 agonist; and MSU, NLRP3 agonist) for 6-8 h, DC functional phenotypes were detected by flow cytometry (Fig. 3A and 3B). We found that both the CD80 and CD86 expression levels were down-regulated in SiNLRP3 DCs compared to the control, which indicated an important role for NLRP3 in DC activation. Without LM stimulation, CD80 and CD86 levels were increased in the MSU-treated group, and a higher expression occurred with MSU treatment combined with LPS and MDP. More significant changes were observed in the LM-stimulated groups; the combination of agonists led to significant up-regulation in LM-induced DC maturation.

Bottom Line: Additionally, the Lmdd-MPFG vaccine caused maturation of DCs in vitro.We demonstrated the synergistic effect of TLR4 and NLRP3 or NOD1 signaling pathways in LM-induced DC activation.These results suggest that the Lmdd-MPFG vaccine is a feasible strategy for preventing HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China.

ABSTRACT
Immunotherapy is a promising treatment for liver cancer. Here, we tested the ability of the attenuated hepatocellular carcinoma-specific Listeria vaccine (Lmdd-MPFG) to treat hepatocellular carcinoma (HCC) in a mouse model. Immunization with the vaccine caused a strong anti-tumor response, especially in mice reinfused with dendritic cells (DCs). In mice that were also administered DCs, tumor suppression was accompanied by the strongest cytotoxic T lymphocyte response of all treatment groups and by induced differentiation of CD4+ T cells, especially Th17 cells. Additionally, the Lmdd-MPFG vaccine caused maturation of DCs in vitro. We demonstrated the synergistic effect of TLR4 and NLRP3 or NOD1 signaling pathways in LM-induced DC activation. These results suggest that the Lmdd-MPFG vaccine is a feasible strategy for preventing HCC.

No MeSH data available.


Related in: MedlinePlus