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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

Combined DC and LM treatment increases immune system effects in spleenSPCs were extracted from tumor-bearing mice of each vaccination groups (n=5), pooled and stained for DC or T cell markers. CD80 and CD86 expression and frequency of mature DCs in the SPCs were analyzed by flow cytometric analysis of cells from the vaccinated or control group, and the peak with gray filled represents the PBS group as control (A and B). CD4+ and CD8+ T cells in SPCs were detected by flow cytometric analysis, and the frequencies of each were analyzed in histograms (C and D). Each data point represents the mean ± SEM from at least three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).
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Figure 5: Combined DC and LM treatment increases immune system effects in spleenSPCs were extracted from tumor-bearing mice of each vaccination groups (n=5), pooled and stained for DC or T cell markers. CD80 and CD86 expression and frequency of mature DCs in the SPCs were analyzed by flow cytometric analysis of cells from the vaccinated or control group, and the peak with gray filled represents the PBS group as control (A and B). CD4+ and CD8+ T cells in SPCs were detected by flow cytometric analysis, and the frequencies of each were analyzed in histograms (C and D). Each data point represents the mean ± SEM from at least three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).

Mentions: To explore the DC-mediated effects under LM infection in vivo, we obtained mouse spleen mononuclear lymphocytes (SPCs) from each group as described above. Functional DCs were detected by flow cytometry (Fig. 5A and Fig. 5B). In the DC+LM group, the percentage of functional DCs in spleen was increased compared to the percentages in other groups. In addition, we examined the percentages of CD4+ and CD8+ T cells induced in spleen mononuclear lymphocytes. As indicated by the data shown in Fig. 5C and Fig. 5D, in the spleen, either the percentage of CD4+T or CD8+T cells was up-regulated, especially CD4+ T cells. Thus, we speculate that DCs are necessary to improve LM immunity in the spleen.


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)

Combined DC and LM treatment increases immune system effects in spleenSPCs were extracted from tumor-bearing mice of each vaccination groups (n=5), pooled and stained for DC or T cell markers. CD80 and CD86 expression and frequency of mature DCs in the SPCs were analyzed by flow cytometric analysis of cells from the vaccinated or control group, and the peak with gray filled represents the PBS group as control (A and B). CD4+ and CD8+ T cells in SPCs were detected by flow cytometric analysis, and the frequencies of each were analyzed in histograms (C and D). Each data point represents the mean ± SEM from at least 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 5: Combined DC and LM treatment increases immune system effects in spleenSPCs were extracted from tumor-bearing mice of each vaccination groups (n=5), pooled and stained for DC or T cell markers. CD80 and CD86 expression and frequency of mature DCs in the SPCs were analyzed by flow cytometric analysis of cells from the vaccinated or control group, and the peak with gray filled represents the PBS group as control (A and B). CD4+ and CD8+ T cells in SPCs were detected by flow cytometric analysis, and the frequencies of each were analyzed in histograms (C and D). Each data point represents the mean ± SEM from at least three independent experiments (*p<0.05, **p<0.01, ***p< 0.001).
Mentions: To explore the DC-mediated effects under LM infection in vivo, we obtained mouse spleen mononuclear lymphocytes (SPCs) from each group as described above. Functional DCs were detected by flow cytometry (Fig. 5A and Fig. 5B). In the DC+LM group, the percentage of functional DCs in spleen was increased compared to the percentages in other groups. In addition, we examined the percentages of CD4+ and CD8+ T cells induced in spleen mononuclear lymphocytes. As indicated by the data shown in Fig. 5C and Fig. 5D, in the spleen, either the percentage of CD4+T or CD8+T cells was up-regulated, especially CD4+ T cells. Thus, we speculate that DCs are necessary to improve LM immunity in the spleen.

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