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Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.

Feng E, Gao H, Su W, Yu C - Neural Regen Res (2012)

Bottom Line: Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone.The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Fuxing Hospital, Capital Medical University, Beijing 100038, China.

ABSTRACT
Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone. In this study, we established a novel vaccine procedure in rats, using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors. On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis. The survival rate of rats bearing C6 glioma was observed. Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma, and induced a strong cytolytic T lymphocyte response in rats. The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period. Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

No MeSH data available.


Related in: MedlinePlus

Morphology of cultured dendritic cells.(A) On day 5, clusters of developing dendritic cells were observed (× 4, light microscopy).(B) On day 9, floating cells were observed (× 10, light microscopy).By scanning electrography at 7 days after culture, cultured dendritic cells had typical long cytoplasmic dendrites (C, ×5 000; D, × 7 000, electron microscopy).
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Figure 1: Morphology of cultured dendritic cells.(A) On day 5, clusters of developing dendritic cells were observed (× 4, light microscopy).(B) On day 9, floating cells were observed (× 10, light microscopy).By scanning electrography at 7 days after culture, cultured dendritic cells had typical long cytoplasmic dendrites (C, ×5 000; D, × 7 000, electron microscopy).

Mentions: On day 5, clusters of developing dendritic cells were evident by light microscopy (Figure 1A). On day 9, floating cells were observed and these cells were considered mature bone marrow-derived DCs (Figure 1B, supplementary Figure 1 online). On day 7, cultured DCs had typical long cytoplasmic dendrites as observed by scanning electron microscopy (Figures 1C, D). By day 9 of DC culture, double immunocytochemistry staining demonstrated the expression of OX6 and OX62 was positive, and flow cytometric analysis showed that 83.4% of DCs were positive for OX62, whereas 80.5% were positive for OX6 (Figure 2).


Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.

Feng E, Gao H, Su W, Yu C - Neural Regen Res (2012)

Morphology of cultured dendritic cells.(A) On day 5, clusters of developing dendritic cells were observed (× 4, light microscopy).(B) On day 9, floating cells were observed (× 10, light microscopy).By scanning electrography at 7 days after culture, cultured dendritic cells had typical long cytoplasmic dendrites (C, ×5 000; D, × 7 000, electron microscopy).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308782&req=5

Figure 1: Morphology of cultured dendritic cells.(A) On day 5, clusters of developing dendritic cells were observed (× 4, light microscopy).(B) On day 9, floating cells were observed (× 10, light microscopy).By scanning electrography at 7 days after culture, cultured dendritic cells had typical long cytoplasmic dendrites (C, ×5 000; D, × 7 000, electron microscopy).
Mentions: On day 5, clusters of developing dendritic cells were evident by light microscopy (Figure 1A). On day 9, floating cells were observed and these cells were considered mature bone marrow-derived DCs (Figure 1B, supplementary Figure 1 online). On day 7, cultured DCs had typical long cytoplasmic dendrites as observed by scanning electron microscopy (Figures 1C, D). By day 9 of DC culture, double immunocytochemistry staining demonstrated the expression of OX6 and OX62 was positive, and flow cytometric analysis showed that 83.4% of DCs were positive for OX62, whereas 80.5% were positive for OX6 (Figure 2).

Bottom Line: Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone.The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Fuxing Hospital, Capital Medical University, Beijing 100038, China.

ABSTRACT
Immunotherapy may be used for the treatment of glioblastoma multiforme; however, the induced immune response is inadequate when either T cells or dendritic cells are used alone. In this study, we established a novel vaccine procedure in rats, using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors. On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis. The survival rate of rats bearing C6 glioma was observed. Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma, and induced a strong cytolytic T lymphocyte response in rats. The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period. Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.

No MeSH data available.


Related in: MedlinePlus