Abstract
Emerging studies suggest that extracellular vesicles (EVs) mediating intercellular communication in the tumor microenvironment (TME) play a key role in driving cancer progression. Tumor-derived small EVs or exosomes (TEX) enriched in immunosuppressive proteins or in microRNAs targeting suppressive pathways in recipient cells contribute to reprogramming the TME into a cancer-promoting milieu. The adenosinergic pathway is an acknowledged major contributor to tumor-induced immune suppression. TEX carry the components of this pathway and utilize ATP to produce adenosine (ADO). TEX-associated ADO emerges as a key factor in the suppression of T cell responses to therapy. Here, the significance of the ADO pathway in TEX is discussed as a highly effective mechanism of cancer-driven immune cell suppression and of resistance to immune therapies.
Highlights
Immune suppression of the adaptive and innate anti-tumor response is an acknowledged contributor to cancer progression [1]
The recent success of immunotherapy with check point inhibitors (ICI) has shown that even a partial restoration of anti-tumor immune responses in patients with cancer leads to long-term survival in responders [2,3]
Only a subset of cancer patients ranging from 20–50% of those treated are responders to ICI therapies [4,5]
Summary
Immune suppression of the adaptive and innate anti-tumor response is an acknowledged contributor to cancer progression [1]. In the last two decades, an extensive volume of data has emerged that has illuminated an enormous complexity of the TME, its heterogeneity in different tumor types and its unique characteristics that shape tumor development and progression in every cancer patient. The key role of intercellular communication within the TME as the major mechanism driving tumor progression has emerged, and understanding of the crosstalk between various immune and tissue cells has become the major goal of cancer research. EVs produced by the tumor and by immune as well as non-immune cells residing in the TME have become an object of intense interest, and numerous studies evaluating their role in shaping innate and adaptive immune responses in cancer are in progress
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