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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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BMDCs phenotype. Levels of molecules of the major histocompatibility complex II (MHCII), CD40, CD80, CD86, and IL-12 in BMDCs were measured after different treatments: control (without treatment: WT), LPS, GK-1, TNFα, TNFα/GK-1. Treatment with LPS, TNFα, and TNFα/GK-1 induces increased expression of MHCII, CD40, CD80, and CD86. When BMDCs were treated only with GK-1 an increase in the production of IL-12 was found. (a) Mean fluorescence intensity (MIF) of MHCII. *P < 0.05, ***P < 0.001. (b) BMDCs phenotype after 10 days of differentiation. 91.9% differentiation was induced (91.9% of CD11c+ cells). Red: isotype control. Blue: BMDCs. (c) Percentage of CD40+ BMDCs after treatment. *P < 0.05. (d). MFI of CD40 in BMDCs. **P < 0.001, ***P < 0.0001. (e) Percentage of CD86+ BMDCs. *P < 0.05, **P < 0.001. (f) MFI of CD86 in BMDCs. *P < 0.05, **P < 0.001, cP < 0.05 TNFα versus GK-1. (g) Percentage of CD80+ BMDCs. *P < 0.05. (h) MFI of CD80 in BMDCs. ANOVA, Tukey. ***P < 0.0001, cP < 0.0001 TNF/GK-1 versus GK-1, +P < 0.0001 TNF versus GK-1. (i) Percentage of IL-12+ BMDCs. (j) MFI of IL-12 in BMDCs. *P < 0.05, **P < 0.001, ***P < 0.0001. Mean ± SEM n ≥ 3.
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fig1: BMDCs phenotype. Levels of molecules of the major histocompatibility complex II (MHCII), CD40, CD80, CD86, and IL-12 in BMDCs were measured after different treatments: control (without treatment: WT), LPS, GK-1, TNFα, TNFα/GK-1. Treatment with LPS, TNFα, and TNFα/GK-1 induces increased expression of MHCII, CD40, CD80, and CD86. When BMDCs were treated only with GK-1 an increase in the production of IL-12 was found. (a) Mean fluorescence intensity (MIF) of MHCII. *P < 0.05, ***P < 0.001. (b) BMDCs phenotype after 10 days of differentiation. 91.9% differentiation was induced (91.9% of CD11c+ cells). Red: isotype control. Blue: BMDCs. (c) Percentage of CD40+ BMDCs after treatment. *P < 0.05. (d). MFI of CD40 in BMDCs. **P < 0.001, ***P < 0.0001. (e) Percentage of CD86+ BMDCs. *P < 0.05, **P < 0.001. (f) MFI of CD86 in BMDCs. *P < 0.05, **P < 0.001, cP < 0.05 TNFα versus GK-1. (g) Percentage of CD80+ BMDCs. *P < 0.05. (h) MFI of CD80 in BMDCs. ANOVA, Tukey. ***P < 0.0001, cP < 0.0001 TNF/GK-1 versus GK-1, +P < 0.0001 TNF versus GK-1. (i) Percentage of IL-12+ BMDCs. (j) MFI of IL-12 in BMDCs. *P < 0.05, **P < 0.001, ***P < 0.0001. Mean ± SEM n ≥ 3.

Mentions: The BMDCs were differentiated from bone marrow cultures of C57BL/6 mice with GM-CSF. 90% of the differentiated cells expressed the CD11c/MHCII+ phenotype (Figure 1(b)).


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)

BMDCs phenotype. Levels of molecules of the major histocompatibility complex II (MHCII), CD40, CD80, CD86, and IL-12 in BMDCs were measured after different treatments: control (without treatment: WT), LPS, GK-1, TNFα, TNFα/GK-1. Treatment with LPS, TNFα, and TNFα/GK-1 induces increased expression of MHCII, CD40, CD80, and CD86. When BMDCs were treated only with GK-1 an increase in the production of IL-12 was found. (a) Mean fluorescence intensity (MIF) of MHCII. *P < 0.05, ***P < 0.001. (b) BMDCs phenotype after 10 days of differentiation. 91.9% differentiation was induced (91.9% of CD11c+ cells). Red: isotype control. Blue: BMDCs. (c) Percentage of CD40+ BMDCs after treatment. *P < 0.05. (d). MFI of CD40 in BMDCs. **P < 0.001, ***P < 0.0001. (e) Percentage of CD86+ BMDCs. *P < 0.05, **P < 0.001. (f) MFI of CD86 in BMDCs. *P < 0.05, **P < 0.001, cP < 0.05 TNFα versus GK-1. (g) Percentage of CD80+ BMDCs. *P < 0.05. (h) MFI of CD80 in BMDCs. ANOVA, Tukey. ***P < 0.0001, cP < 0.0001 TNF/GK-1 versus GK-1, +P < 0.0001 TNF versus GK-1. (i) Percentage of IL-12+ BMDCs. (j) MFI of IL-12 in BMDCs. *P < 0.05, **P < 0.001, ***P < 0.0001. Mean ± SEM n ≥ 3.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230216&req=5

fig1: BMDCs phenotype. Levels of molecules of the major histocompatibility complex II (MHCII), CD40, CD80, CD86, and IL-12 in BMDCs were measured after different treatments: control (without treatment: WT), LPS, GK-1, TNFα, TNFα/GK-1. Treatment with LPS, TNFα, and TNFα/GK-1 induces increased expression of MHCII, CD40, CD80, and CD86. When BMDCs were treated only with GK-1 an increase in the production of IL-12 was found. (a) Mean fluorescence intensity (MIF) of MHCII. *P < 0.05, ***P < 0.001. (b) BMDCs phenotype after 10 days of differentiation. 91.9% differentiation was induced (91.9% of CD11c+ cells). Red: isotype control. Blue: BMDCs. (c) Percentage of CD40+ BMDCs after treatment. *P < 0.05. (d). MFI of CD40 in BMDCs. **P < 0.001, ***P < 0.0001. (e) Percentage of CD86+ BMDCs. *P < 0.05, **P < 0.001. (f) MFI of CD86 in BMDCs. *P < 0.05, **P < 0.001, cP < 0.05 TNFα versus GK-1. (g) Percentage of CD80+ BMDCs. *P < 0.05. (h) MFI of CD80 in BMDCs. ANOVA, Tukey. ***P < 0.0001, cP < 0.0001 TNF/GK-1 versus GK-1, +P < 0.0001 TNF versus GK-1. (i) Percentage of IL-12+ BMDCs. (j) MFI of IL-12 in BMDCs. *P < 0.05, **P < 0.001, ***P < 0.0001. Mean ± SEM n ≥ 3.
Mentions: The BMDCs were differentiated from bone marrow cultures of C57BL/6 mice with GM-CSF. 90% of the differentiated cells expressed the CD11c/MHCII+ phenotype (Figure 1(b)).

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