Transcriptomics

Dataset Information

0

Antitumor therapeutic vaccination induces immunosuppressive dendritic cells


ABSTRACT: Vaccination induces immunostimulatory signals which are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Thus, here we characterized IL-10-producing cells treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1. These IL-10+ DC showed impaired in vitro T-cell stimulatory capacity, which was rescued by incubation with IL-10R and PD-L1-inhibiting antibodies. In vivo IL-10 blockade during vaccination decreased the proportion of IL-10+ DC and improved their maturation, without modifying PD-L1 expression. Similarly, PD-L1 blockade did not affect IL-10 expression, suggesting independent regulation of these molecules. Interestingly, vaccination combined with simultaneous blockade of IL-10 and PD-L1 induced stronger immune responses, resulting in a higher therapeutic efficacy in tumor-bearing mice. These results show that vaccine-induced immunoregulatory DC with dual expression of IL-10 and PD-L1 impair priming of antitumor immunity, suggesting that therapeutic vaccination protocols may benefit from combined targeting of these molecules.

ORGANISM(S): Mus musculus

PROVIDER: GSE84980 | GEO | 2017/06/10

SECONDARY ACCESSION(S): PRJNA335803

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2017-04-03 | GSE92852 | GEO
2023-05-22 | GSE232730 | GEO
2024-02-09 | GSE247304 | GEO
2023-09-01 | GSE222080 | GEO
2024-03-30 | GSE242860 | GEO
2024-06-22 | PXD050744 | Pride
2019-08-20 | GSE135976 | GEO
2021-01-01 | GSE164093 | GEO
2019-04-18 | GSE130008 | GEO
2021-08-26 | GSE165850 | GEO