Co-immunizing with PD-L1 induces CD8+ DCs-mediated anti-tumor immunity in multiple myeloma.
Int Immunopharmacol
; 84: 106516, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32334387
ABSTRACT
Tumor therapeutic vaccines have faced a challenge for effective protection against malignant tumors by inducing tumor-specific CD8+ T cell responses. Here, we designed a DNA vaccine containing a tumor-specific antigen of Dickkopf-1 (DKK-1) and an immune checkpoint of programmed death ligand 1 (PD-L1) delivered by PLGA/PEI nanoparticle-mediated delivery system for multiple myeloma therapy. Murine subcutaneous tumor model established with human DKK1 (hDKK-1)-SP2/0 cells were intramuscularly immunized with PLGA/PEI-pPD-L1/pDDK-1 vaccine and equal amount of control 3 times at 10 day-intervals. Compared with PLGA/PEI-pDKK1 immunization group, PLGA/PEI-pPD-L1/pDKK-1 co-immunization enhanced the induction and mature of CD11c+ DCs and CD8+CD11c+ DCs, and promoted antigen-specific Th1 responses and cytotoxic T lymphocyte (CTL) responses. The reduced tumor volume and weight as well as increased tumor inhibition rate were observed in PLGA/PEI-pPD-L1/pDKK-1 vaccine co-immunization group, indicated that the vaccine could effectively inhibit the tumor growth of multiple myeloma. The anti-tumor activity of PLGA/PEI-pPD-L1/pDKK-1 vaccine was abrogated by CD8 cell depletion accompanied with the reduced percentages of CD8+CD11c+ DCs and CD8+ T cells in the spleen and TILs. These results indicated that the anti-tumor efficacy of PLGA/PEI-pPD-L1/pDKK-1 vaccine was required for CD8+CD11c+ DCs-mediated CD8+ T cell immunity responses. This vaccine strategy may represent a potential and promising approach for hematological malignancy treatment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Linfócitos T CD8-Positivos
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Vacinas de DNA
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Peptídeos e Proteínas de Sinalização Intercelular
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Antígeno B7-H1
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Mieloma Múltiplo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
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FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article