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Purine Metabolites in Tumor-Derived Exosomes May Facilitate Immune Escape of Head and Neck Squamous Cell Carcinoma

Ludwig, Nils and Gillespie, Delbert G. and Reichert, Torsten E. and Jackson, Edwin K. and Whiteside, Theresa L. (2020) Purine Metabolites in Tumor-Derived Exosomes May Facilitate Immune Escape of Head and Neck Squamous Cell Carcinoma. Cancers, 12 (6). p. 1602. ISSN 2072-6694

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Body fluids of patients with head and neck squamous cell carcinoma (HNSCC) are enriched in exosomes that reflect properties of the tumor. The aim of this study was to determine whether purine metabolites are carried by exosomes and evaluate their role as potential contributors to tumor immune escape. The gene expression levels of the purine synthesis pathway were studied using the Cancer Genome Atlas (TCGA) Head and Neck Cancer database. Exosomes were isolated from supernatants of UMSCC47 cells and from the plasma of HNSCC patients (n = 26) or normal donors (NDs; n = 5) using size exclusion chromatography. Ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to assess levels of 19 purine metabolites carried by exosomes. In HNSCC tissues, expression levels of genes involved in the purinergic pathway were upregulated indicating an accelerated purine metabolism compared to normal tissues. Exosomes from supernatants of UMSCC47 cells contained several purine metabolites, predominantly adenosine and inosine. Purine metabolite levels were enriched in exosomes isolated from the plasma of HNSCC patients compared to those isolated from NDs and carried elevated levels of adenosine (p = 0.0223). Exosomes of patients with early-stage disease and no lymph node metastasis contained significantly elevated levels of adenosine and 5′-GMP (p = 0.0247 and p = 0.0229, respectively). The purine metabolite levels in exosomes decreased in patients with advanced cancer and nodal involvement. This report provides the first evidence that HNSCC cells shuttle purine metabolites in exosomes, with immunosuppressive adenosine being the most prominent purine. Changes in the content and levels of purine metabolites in circulating exosomes reflect disease progression in HNSCC patients


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Ludwig, Nils
Gillespie, Delbert G.dgg3@pitt.edudgg30000-0001-8110-6170
Reichert, Torsten E.
Jackson, Edwin K.edj@pitt.eduedj0000-0002-8101-6009
Whiteside, Theresa L.whitesidetl@upmc.edu0000-0001-7316-6181
Date: 15 June 2020
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 12
Number: 6
Publisher: MDPI AG
Page Range: p. 1602
DOI or Unique Handle: 10.3390/cancers12061602
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Uncontrolled Keywords: exosomes, extracellular vesicles, TEX, HNSCC, head and neck cancer, purine metabolites
ISSN: 2072-6694
Official URL:
Funders: National Institutes of Health, Leopoldina Fellowships, German National Academy of Sciences Leopoldina
Article Type: Research Article
Date Deposited: 14 Jun 2021 18:31
Last Modified: 14 Jun 2021 18:31


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