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GK-1 improves the immune response induced by bone marrow dendritic cells loaded with MAGE-AX in mice with melanoma.

Piñón-Zárate G, Herrera-Enríquez MÁ, Hernández-Téllez B, Jarquín-Yáñez K, Castell-Rodríguez AE - J Immunol Res (2014)

Bottom Line: Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response.Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes.Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Inmunoterapia e Ingeniería de Tejidos, Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México Edificio A, Sexto Piso, Ciudad Universitaria, Avenida Universidad No. 3000, Ciudad de México 04510DF, Mexico.

ABSTRACT
The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

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Cytokine profile. Percentage of total CD8 T cells and IFNγ or IL-10 producing CD8 cells, in peritumoral lymph nodes of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. Mice treated with BMDCs MAGE/GK-1 showed increased levels of IFNγ in CD8+ lymphocytes. (a) Percentage of total CD8 T cells and IFNγ and IL-10 producers. *P < 0.05 GK-1 versus all groups. (b) MFI of IFNγ and IL-10 in CD8 T lymphocytes. *P < 0.05, cP < 0.05 GK-1 versus MAGE, +P < 0.05 MAGE/GK-1 versus MAGE. Without treatment (WT). Mean ± SEM n ≥ 3.
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fig5: Cytokine profile. Percentage of total CD8 T cells and IFNγ or IL-10 producing CD8 cells, in peritumoral lymph nodes of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. Mice treated with BMDCs MAGE/GK-1 showed increased levels of IFNγ in CD8+ lymphocytes. (a) Percentage of total CD8 T cells and IFNγ and IL-10 producers. *P < 0.05 GK-1 versus all groups. (b) MFI of IFNγ and IL-10 in CD8 T lymphocytes. *P < 0.05, cP < 0.05 GK-1 versus MAGE, +P < 0.05 MAGE/GK-1 versus MAGE. Without treatment (WT). Mean ± SEM n ≥ 3.

Mentions: No significant differences were found in the percentage of CD8 T lymphocytes in lymph nodes peripheral to the tumor (Figure 5(a)). In terms of cytokine production, in CD8 T lymphocytes, the TNFα, TNFα/GK-1, and TNFα/MAGE-AX/GK-1 groups showed increased production of IFNγ compared to the WT group and TNFα/MAGE-AX BMDCs; however, groups treated with TNFα/MAGE-AX/GK-1 and TNFα/GK-1 BMDCs showed a higher IFNγ production than the TNFα group (Figure 5(b)). Finally, in the case of IL-10, the GK-1 group showed a significant increase in the percentage of CD8 IL-10+ T cells in comparison to the TNFα/MAGE-AX, TNFα/GK-1, and TNFα/MAGE-AX/GK-1 groups (Figure 5(a)). No changes were observed in the IL-10 MFI (Figure 5(b)). It is important to note that the higher levels of fluorescence were showed by IFNγ in CD8+ T lymphocytes (Figure 5(b)), in comparison with IL-10, although the group treated with TNFα/GK-1 BMDCs showed a significant increase in the percentage of CD8 IL-10+ T lymphocytes in comparison to the other groups (Figure 5(a)).


GK-1 improves the immune response induced by bone marrow dendritic cells loaded with MAGE-AX in mice with melanoma.

Piñón-Zárate G, Herrera-Enríquez MÁ, Hernández-Téllez B, Jarquín-Yáñez K, Castell-Rodríguez AE - J Immunol Res (2014)

Cytokine profile. Percentage of total CD8 T cells and IFNγ or IL-10 producing CD8 cells, in peritumoral lymph nodes of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. Mice treated with BMDCs MAGE/GK-1 showed increased levels of IFNγ in CD8+ lymphocytes. (a) Percentage of total CD8 T cells and IFNγ and IL-10 producers. *P < 0.05 GK-1 versus all groups. (b) MFI of IFNγ and IL-10 in CD8 T lymphocytes. *P < 0.05, cP < 0.05 GK-1 versus MAGE, +P < 0.05 MAGE/GK-1 versus MAGE. Without treatment (WT). Mean ± SEM n ≥ 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230216&req=5

fig5: Cytokine profile. Percentage of total CD8 T cells and IFNγ or IL-10 producing CD8 cells, in peritumoral lymph nodes of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. Mice treated with BMDCs MAGE/GK-1 showed increased levels of IFNγ in CD8+ lymphocytes. (a) Percentage of total CD8 T cells and IFNγ and IL-10 producers. *P < 0.05 GK-1 versus all groups. (b) MFI of IFNγ and IL-10 in CD8 T lymphocytes. *P < 0.05, cP < 0.05 GK-1 versus MAGE, +P < 0.05 MAGE/GK-1 versus MAGE. Without treatment (WT). Mean ± SEM n ≥ 3.
Mentions: No significant differences were found in the percentage of CD8 T lymphocytes in lymph nodes peripheral to the tumor (Figure 5(a)). In terms of cytokine production, in CD8 T lymphocytes, the TNFα, TNFα/GK-1, and TNFα/MAGE-AX/GK-1 groups showed increased production of IFNγ compared to the WT group and TNFα/MAGE-AX BMDCs; however, groups treated with TNFα/MAGE-AX/GK-1 and TNFα/GK-1 BMDCs showed a higher IFNγ production than the TNFα group (Figure 5(b)). Finally, in the case of IL-10, the GK-1 group showed a significant increase in the percentage of CD8 IL-10+ T cells in comparison to the TNFα/MAGE-AX, TNFα/GK-1, and TNFα/MAGE-AX/GK-1 groups (Figure 5(a)). No changes were observed in the IL-10 MFI (Figure 5(b)). It is important to note that the higher levels of fluorescence were showed by IFNγ in CD8+ T lymphocytes (Figure 5(b)), in comparison with IL-10, although the group treated with TNFα/GK-1 BMDCs showed a significant increase in the percentage of CD8 IL-10+ T lymphocytes in comparison to the other groups (Figure 5(a)).

Bottom Line: Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response.Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes.Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Inmunoterapia e Ingeniería de Tejidos, Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México Edificio A, Sexto Piso, Ciudad Universitaria, Avenida Universidad No. 3000, Ciudad de México 04510DF, Mexico.

ABSTRACT
The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

Show MeSH
Related in: MedlinePlus