Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration.

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As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and noncoding RNA to cells within the tumor microenvironment. Here, we quantified the RNA payload within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function. Exosomes derived from B16F0 melanoma cells were enriched for a subset of coding and noncoding RNAs that did not reflect the abundance in the parental cell. Upon exosome delivery, RNAseq revealed the dynamic changes in the transcriptome of CTLL2 cytotoxic T cells. In analyzing transiently coexpressed gene clusters, pathway enrichment suggested that the B16F0 exosomal payload altered mitochondrial respiration, which was confirmed independently, and upregulated genes associated with the Notch signaling pathway. Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels.\nDATABASES: Gene expression data are available in the GEO database under the accession SuperSeries number GSE102951.", "claims": [{"id": "claim-target-result", "statement": "B16F0 exosomes delivered an mRNA payload that altered the CTLL2 cytotoxic T-cell transcriptome, increased mitochondrial respiration and activated Notch-associated expression, whereas exosomal miRNA showed no systematic reduction of target-mRNA abundance. The study used DESeq2 for differential transcript analysis and a Welch t-test to identify miRNAs detected above background. The underlying gene-expression data are accessible through GEO SuperSeries accession GSE102951.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29399967", "locator": "sections[1] \"Introduction\" paragraph 3", "quote": "In short, the transcriptional landscape reflected the delivery of an exosomal mRNA payload while exosomal miRNA appeared to have no effect on transcript abundance."}, {"asset": "source:pmid:29399967", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "B16F0 exosomes delivered an mRNA payload that altered the CTLL2 cytotoxic T-cell transcriptome, increased mitochondrial respiration and activated Notch-associated expression, whereas exosomal miRNA showed no systematic reduction of target-mRNA abundance. The study used DESeq2 for differential transcript analysis and a Welch t-test to identify miRNAs detected above background. The underlying gene-expression data are accessible through GEO SuperSeries accession GSE102951.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29399967"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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