Page 495 - Read Online

Page 4 of 9 Pastor et al. J Cancer Metastasis Treat 2020;6:39 I http://dx.doi.org/10.20517/2394-4722.2020.57
[23]
cause an expansion of the metastatic lesion . In addition, it is time-consuming since several surgeries
[9]
are needed to follow up on tumor progression, making it more expensive . Exosomes are steady in the
circulation and are found in almost every body fluid which makes them easy to use as a diagnostic tool. In
comparison to tissue biopsy, liquid biopsy has the advantage of being a non-invasive method, which allows
real-time monitoring of disease progression as well as detection of any tumor in any anatomical location
with no risk of augmenting the metastatic lesion. Moreover, it improves the chance of an early diagnosis of
cancer. Exosomes are presently emerging as promising non-invasive biomarkers of tumor progression and
promotion of malignancy.

In the circulatory system of a patient with HNSCC, circulating tumor DNA (ctDNA, from tumor cells) is
[25]
detected [4,24] . ctDNA may be detected in various body fluids . During the formation of a tumor, circulating
tumor cells (CTC) can be detected in the bloodstream through different techniques, which allows CTC
lines to be used for drug sensitivity analysis and extraction of information at the cellular level [4,26] . Therefore,
CTC and ctDNA can be used as a diagnostic tool for real-time monitoring of tumor progression. However,
it requires fresh samples, demands larger amounts of blood and requires the processing of samples within
hours.

The advantage of exosomes is that one can use not only fresh samples but frozen samples as well. Thus,
we were able to conduct exosome analyses on long-term frozen samples from a vaccination trial. It was
[27]
possible to show the antitumor response and correlate the results with the patients’ survival . Exosomes
among other cancer-related particles are present in higher concentrations and are detectable earlier in
metastatic disease than CTCs . As a result, another considerable advantage of exosomes is the small
[28]
amount of blood needed to detect exosomes. Around one milliliter of blood may be enough depending
on the extent of the analyses planned. Exosomes are more profuse and more specific since they contain
[12]
highly informative protein content and genetic cargo such as DNA and mRNA . Besides, exosomes
reveal specific markers such as HSP70 and Alix. They can reveal the original cell markers by imagining
particular surface proteins and their target cells, making the isolation easy for tissue and target cell-specific
[29]
exosomes . The content of nucleic acids in exosomes is a qualified source for cancer analysis. The DNA
[29]
content of exosomes can reveal the mutational status of the original cell .
HNSCC patients during an active disease state show a significant rise in circulating exosomes with
exceptionally high levels of TEX and immunosuppressive factors [7,30] . Not only TEX but also T-cell derived
[31]
exosomes bear comparatively high levels of immunosuppressive factors in HNSCC patients . In case
of advanced disease (stage III/IV), T-cell derived exosomes conveyed much higher levels of CD15s, a
[31]
functional Treg marker, than in patients in the first stage . This is another indicator that plasma-derived
exosomes of HNSCC patients could function as an easily accessible, non-invasive “liquid biopsy” of disease
progression.

There is a way to transport drugs to cells since exosomes are taken up by various cells. Packaging paclitaxel
[32]
in exosomes facilitates the allocation of the pharmacological agent . Many more studies are needed
regarding this issue, and time will reveal which of these approaches will lead to a better outcome in patient
care.

The disadvantage might be that the enhancement of exosomes by ultracentrifugation, ultrafiltration, or
density gradient centrifugation is not only time-consuming but also requires considerable equipment, thus
being cost-intensive . In the future, faster isolation methods should be developed for clinical application
[29]
and standardization of results and diagnostic reference levels as well.