Ontology highlight
ABSTRACT:
PROVIDER: PRJNA936169 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23558317_1.fastq.gz | Fastqsanger.gz | |||
| SRR23558317_2.fastq.gz | Fastqsanger.gz | |||
| SRR23558318_1.fastq.gz | Fastqsanger.gz | |||
| SRR23558318_2.fastq.gz | Fastqsanger.gz | |||
| SRR23558319_1.fastq.gz | Fastqsanger.gz |
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Project description:Sipuleucel-T (sip-T) is the only FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Here, we report the first high-dimensional analyses of sip-T using mass cytometry (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median ~60%) of sip-T, followed by B-cells, and natural killer (NK) and NKT cells. We hypothesized that treatment of sip-T with homeostatic cytokines known to activate/expand effector lymphocytes could augment efficacy against prostate cancer. Of cytokines tested, IL-15 treated sip-T showed the most significant activation/proliferation of effector lymphocytes in an antigen-specific manner, as well as augmentation of tumor cytotoxicity in-vitro. Adoptive transfer of IL-15 treated sip-T into NSG mice resulted in potent prostate tumor growth inhibition compared with control sip-T. Evaluation of tumor-infiltrating lymphocytes revealed a two-to-fourteen-fold higher influx of sip-T and a significant increase in interferon (IFN)-γ producing CD8+ T and NKT cells within the tumor microenvironment (TME) in the IL-15 group.
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