Ontology highlight
ABSTRACT:
PROVIDER: PRJNA744256 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15055303_1.fastq.gz | Fastqsanger.gz | |||
| SRR15055303_2.fastq.gz | Fastqsanger.gz | |||
| SRR15055304_1.fastq.gz | Fastqsanger.gz | |||
| SRR15055304_2.fastq.gz | Fastqsanger.gz | |||
| SRR15055305_1.fastq.gz | Fastqsanger.gz |
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Project description:The neoadjuvant immune checkpoint blockade therapy only benefits a limited fraction of glioblastoma multiforme (GBM) patients. Thus, targeting other immunomodulators on myeloid cells is an attractive therapeutic option. Here, we performed single-cell RNA sequencing and spatial transcriptomics of GBM patients treated with neoadjuvant anti-PD-1 therapy. We identified unique monocyte-derived tumor-associated macrophage (TAM) subpopulations with functional plasticity that highly expressed the immunosuppressive SIGLEC9 gene and preferentially accumulated in the non-responders to anti-PD-1 treatment. Deletion of Siglece (murine homologue) resulted in significantly restrained tumor development and prolonged survival in mouse models. Mechanistically, targeting Siglece directly activated both CD4+ T cells and CD8+ T cells through antigen presentation, secreted chemokines and co-stimulatory factor interactions. Furthermore, Siglece deletion synergized with anti-PD-1/PD-L1 treatment to improve antitumor efficacy. Our data demonstrated that Siglec-9 is an immune checkpoint molecule on macrophages that can be targeted to enhance anti-PD-1/PD-L1 therapeutic efficacy for GBM treatment.
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