PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer.
Cancer Lett
; 406: 27-35, 2017 10 10.
Article
em En
| MEDLINE
| ID: mdl-28797844
ABSTRACT
Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8+T-cells, the majority of these CD8+T-cells expressed PD-1. Moreover, GM-CSF vaccine up-regulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1/PD-L1 blockade to GM-CSF vaccine therapy could significantly increase the population of CD4+ T, CD8+ T and CD8+ IFN-γ+ T but not CD4+ Foxp3+ T-cells and induced the highest production of IFN-γ. PD-1/PD-L1 blockade could effectively rescue the tumor-specific T lymphocytes generated by the GM-CSF vaccine, resulting in consistent tumor rejection. Taken together, PD-1/PD-L1 blockade combined with SA-GM-CSF-modified vaccine could effectively induce a strong specific antitumor immune response against prostate cancer.
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MEDLINE
Assunto principal:
Neoplasias da Próstata
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
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Vacinas Anticâncer
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Estreptavidina
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Antígeno B7-H1
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Receptor de Morte Celular Programada 1
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article