Abstract
Exosomes play a vital role in intercellular communication and their immunomodulatory potential have become an important focus in cancer research. Various methods have been developed for the isolation although each method differs in the number and purity of exosomes they yield. In melanoma, tumor-derived exosomes drive immunosuppression within the tumor microenvironment. The co-elution of exosomes and soluble factors such as cytokines during isolation, however, make it difficult to ascertain the contribution of exosome cargo, as soluble cytokines are equally capable of immune suppression. In this review we will expound upon the biological relevance that exosome-associated cytokines possess. Furthermore, we discuss the technical challenges that arise during exosome isolation and what this means for further studies into the TME and in vivo work.
Highlights
The tumor microenvironment (TME) has been the mainstay of tumor biology research for over 20 years
All methods led to a decrease in the concentration of cytokines detected in exosome isolates compared to the original supernatants, the REIUS method had the greatest impact in reducing the presence of soluble cytokines
IL-8 and IL-10 were present in high concentrations but overall reduction in concentration was seen for all 13 cytokines tested concluding that while REIUS cannot remove all soluble cytokines, they are reduced to a greater extent when compared to other exosome isolation methods, ensuring higher purity without sacrificing exosome yield
Summary
The tumor microenvironment (TME) has been the mainstay of tumor biology research for over 20 years. Exosomes are thought to enhance the specificity of cytokine signals through the presence of receptors such as MHCs, tetraspanins and lactadherins in the exosome membrane, which are important for targeting other cell types [11]. Several cytokines and their receptors including IL-1, MCSF, TGFb, and TNFa have been reported in other studies to exist in both soluble and membrane-bound forms, both which are biologically active [19,20,21,22,23].
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