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.