title: Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function.
abstract: As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T-cell function, a key mechanism for antitumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T-cell proliferation. In contrast, Cloudman S91 exosomes promoted T-cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells. Mechanistically, transcript profiling suggested that exosomal mRNA is enriched for full-length mRNAs that target immune-related pathways. Interestingly, B16F0 exosomes were unique in that they contained both protein and mRNA for PTPN11, which inhibited T-cell proliferation. Collectively, the results suggest that upregulation of PTPN11 by B16F0 exosomes to tumor infiltrating lymphocytes would bypass the extracellular control of the immune checkpoints.
authors.affiliation: Department of Chemical and Biomedical Engineering, WVU Cancer Institute, Morgantown, WV, USA.
authors.forename: Yueting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, USA.
authors.forename: Wentao
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, USA.
authors.forename: Emily Chambers
authors.initials: EC
authors.lastname: McGinley
authors.affiliation: Department of Chemical and Biomedical Engineering, WVU Cancer Institute, Morgantown, WV, USA.|Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Klinke
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D055354:Exosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D008213:Lymphocyte Activation; D008544:Melanocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse
keywords: PTPN11; exosomes; immune checkpoints; intercellular communication; tumor immunology