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Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration
Author(s) -
Bland Cassidy L.,
ByrneHoffman Christi.,
Fernandez Audry,
Rellick Stephanie L.,
Deng Wentao,
Klinke David J.
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14396
Subject(s) - microvesicles , cytotoxic t cell , transcriptome , biology , tumor microenvironment , microbiology and biotechnology , exosome , cancer research , rna , melanoma , cancer immunotherapy , microrna , immune system , immunotherapy , gene expression , gene , immunology , genetics , in vitro
While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. 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 RNA s that did not reflect the abundance in the parental cell. Upon exosome delivery, RNA seq revealed the dynamic changes in the transcriptome of CTLL 2 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 mi RNA appeared to have no systematic effect on downregulating target mRNA levels. Databases Gene expression data are available in the GEO database under the accession SuperSeries number GSE102951 .