A Clinician's Guide to Cancer-Derived Exosomes: Immune Interactions and Therapeutic Implications

Abstract

Understanding of the role of immunity in the regulation of cancer growth continues to rapidly increase. This is fuelled by the impressive results yielded in recent years by immune checkpoint inhibitors, which block regulatory pathways to increase immune-mediated cancer destruction. Exosomes are cell-secreted membranous nanoscale vesicles that play important roles in regulating physiological and pathophysiological processes. Cancer-derived exosomes (CDEXs) and their biologically-active cargos have been proven to have varied effects in malignant progression, including the promotion of angiogenesis, metastasis, and favorable microenvironment modification. More recently, there is an increasing appreciation of their role in immune evasion. In addition to CDEXs, there are immune-derived exosomes that facilitate communication between immune cells in the non-malignant setting. Investigation of cancer-mediated mechanisms behind interruption or modification of these normal exosomal pathways may provide further understanding of how malignant immune evasion is accomplished. Accumulating evidence indicates that immune-active CDEXs also have the potential to impact clinical oncological management. Whilst immune checkpoint inhibitors have well-established pharmacologically-targeted pathways involving the immune system, other widely used treatments such as radiation and cytotoxic chemotherapies do not. Thus, investigating exosomes in immunotherapy is important for the development of next-generation combination therapies. In this article, we review the ways in which CDEXs impact individual immune cell types and how this contributes to the development of immune evasion. We discuss the relevance of lymphocytes and myeloid-lineage cells in the control of malignancy. In addition, we highlight the ways that CDEXs and their immune effects can impact current cancer therapies and the resulting clinical implications.

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

“…Actual studies regarding immune interactions regulating treatment responsiveness, such as studies of exosomes (cancer-derived exosomes, oncosomes) and even their possible use in immune therapies, are increasing [100,101]. Liquid biopsy markers and urinederived information might change the scope of cancer treatment, using new technology with higher sensitivity to acknowledge all of these molecule markers [102][103][104].…”

Cancer neoantigens as potential targets for immunotherapy

“…This may explain the responses seen using immunotherapy for such immunologically active tumors. In addition to the cell-mediated distant metastasis, exosome-mediated metastasis has been recognized as an independent mechanism, and recently has been found to regulate cancer immunity and responses to ICIs [ 29 ]. This knowledge of exosome-mediated metastasis and cancer immunity is important for developing therapeutic strategies to eliminate metastasis and biomarker to monitor tumor and immune responses.…”

Extracellular Vesicles in Oncology: from Immune Suppression to Immunotherapy

“…It is evident from this study that exosomal PD-L2 could also serve as potential biomarker in cancer diagnosis and therapy. Finally, testing of additional ICP proteins on exosomes as predictive liquid biopsy biomarker in cancer patients receiving various ICP inhibitors would improve understanding the molecular mechanisms of resistance and failure to immunotherapy ( 41 , 42 ).…”