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Figure 1. Exosomes and some of their properties with their potential use as diagnostic tools:this figure illustrates tumor cells centrally
surrounded by exosomes, including tumor-derived exosomes (TEX) and some of their properties as prescribed above applicable in
the clinical routine soon. It also shows the diagnostic value and applicability in the clinical routine not yet determined. For example,
TEX participate in the regulation of the epithelial-to-mesenchymal transition (EMT), TEX carrying damage-associated molecular
patterns (DAMPs) may promote cancer progression through stimulation of antiviral pathways, exosomes accumulate in the
tumor microenvironment (TME), and TEX promote immunomodulation. Some typical exosome analyses have been included: TEX
cause a decrease in CD69 in T-cells by flow cytometry (lower left), nanoparticle analyses by Zetaviewer before and after primary
radiochemotherapy in head and neck squamous cell carcinoma (HNSCC) (upper right) and the influence of TEX on the protein
expression profile of p53 in B-cells by dot blots (lower right)

[19]
cells . Exosome features such as the capability to modulate the host immune response, communication
network of exosomes with the tumour microenvironment and involvement of exosomes in tumor
[19]
progression and metastasis show that they play an important role in the tumor microenvironment .
Tumor hypoxia is considered a negative predictive factor in HNSCC [20,21] . Hypoxic cancer cells are
considered to be radioresistant. Interestingly, hypoxia-derived exosomes have been described to express
a different phenotype, and consequently, profile change of exosomes toward hypoxia could be used as a
[22]
biomarker to guide further therapy .

The aspects of exosomes mentioned above given their use as diagnostic tools are summarized in the
following Figure 1.

PROS AND CONS OF EXOSOME USE IN LIQUID BIOPSY
For the assessment of tumor profiling, a tissue biopsy is one of the methods standardly used in which a
sample of tissue is taken from the body by using specific needles or surgery. This procedure is not only
an invasive method, but it also shows the disadvantage that the anatomical location of some oncogenic
mutations is not always accessible by tissue biopsy. Another disadvantage is that the tissue extraction may