Conf 1. Roles of EVs in Cancer

Extracellular Vesicles (EVs)

• EVs are phospholipid-delimited particles released by cells into the extracellular environment.
• EVs transfer content between cells.
• A key function of EVs is transferring cellular components, such as proteins, nucleic acids, lipids and sugars.
• EV heterogeneity includes size, origin, content, and functions.
• A common size range for EVs is 30 nm to ≥5 µm.
• A subtype of EV enriched with CD63 is exosomes.
• EV subtypes include ectosomes, exosomes, apoptotic bodies, and microvesicles.
• A challenge in isolating EVs is overlapping biophysical properties between different subtypes.
• Density gradients, precipitation, and differential ultracentrifugation are common methods used for EV isolation.
• Various molecules, including proteins and nucleic acids, are found in EVs.
• EVs can interact with target cells in several ways. Direct transfer or cargo transfer and receptor-mediated signalling are involved.
• A role of tumor-derived EVs in cancer progression is transferring RNA, cytokines, and growth factors to recipient cells.
• EVs can contribute to metastatic disease by carrying components promoting the invasion and metastasis of cancer cells.
• Another function of EVs is altering the tumor microenvironment, a factor that promotes cancer growth and survival.
• EVs can be biomarkers for cancer because of their nucleic acid and protein contents which are derived from cancer cells.
• Tumor-derived EVs effect the tumor microenvironment (TME) to promote cancer growth and survival.
• They also are used in cancer therapy research to target tumor cell antigens, and suppress immune responses.

EV content and function in Cancer

• Cellular origin, external conditions, and interactions with recipient cells determine EV content.
• Tumor-derived EVs play a major role in cancer progression.
• EVs carry RNA, cytokines and growth factors, influencing recipient cells.
• EVs are associated with metastatic disease development. They promote invasion and metastasis.
• EVs have various effects on tumor microenvironment to either hinder or promote cancer progression and survival.
• The role of EVs in mediating an immune response within the TME can be used.

EV isolation and subtypes

• Factors that influence the content of an EV include the cell of origin, environmental conditions, and interactions with recipient cells.
• EV subtypes, which have specific functions in cancer include ectosomes, exosomes, apoptotic bodies, and microvesicles.
• Common isolation techniques such as density gradients, precipitation techniques, and differential ultracentrifugation, are used to isolate EVs.
• Difficulties associated with studying EV subtypes may include distinct subtypes that overlap in various physical characteristics, limited availability of particular cell lines, and the difficulty in using various imaging techniques.

EVs and Cancer Therapy

• EVs as biomarkers for cancer diagnosis.
• Potential clinical applications of EVs as a way to directly target tumors.
• EVs modulate immune responses by transporting cytokines and PD-L1.
• EVs are significant in cancer therapy research due to their roles in delivering therapeutic agents.

EVs and Immune Cells

• EVs affect tumor-associated macrophages (TAMs).
• EVs that polarize TAMs into M2 macrophages promote tumor growth.
• A role of PD-L1 in EVs is that it plays a key aspect in immunosuppression by exhausting T cells which contributes to tumor growth, immune response, and angiogenesis.