Not all extracellular vesicles were created equal: clinical implications

Ortiz, Alberto

doi:10.21037/atm.2017.01.40

Cited by 28 publications

(26 citation statements)

References 26 publications

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“…Biomarkers of platelet activation in cancer patients are soluble P-selectin, thrombospondin 1, TSP-1, β-thromboglobulin, CD40 ligand, transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), angiopoetin-1 (AP-1), matrix proteins, CCL17, CCXL1, CXCL5, and others [ 2 , 48 , 49 ]. Among the proteins identified on platelet exosomes is GAPDH, which can function as a membrane fusion protein and can serve as a plasmin/ogen receptor along with histone H2B that is also found on exosomes of different cell types [ 50 – 53 ]. This represents an underexplored source of immune suppression, as plasmin can potentially suppress NK cells through the release of fibrin and excessive exosome release could exhaust an NK response [ 10 ].…”

Section: Markers Of Platelet Activation In Cancer Patientsmentioning

confidence: 99%

Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?

Wojtukiewicz

Hempel²,

Sierko

et al. 2017

Cancer Metastasis Rev

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The association between coagulation and cancer development has been observed for centuries. However, the connection between inflammation and malignancy is also well-recognized. The plethora of evidence indicates that among multiple hemostasis components, platelets play major roles in cancer progression by providing surface and granular contents for several interactions as well as behaving like immune cells. Therefore, the anticancer potential of anti-platelet therapy has been intensively investigated for many years. Anti-platelet agents may prevent cancer, decrease tumor growth, and metastatic potential, as well as improve survival of cancer patients. On the other hand, there are suggestions that antiplatelet treatment may promote solid tumor development in a phenomenon described as “cancers follow bleeding.” The controversies around antiplatelet agents justify insight into the subject to establish what, if any, role platelet-directed therapy has in the continuum of anticancer management.

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Section: Markers Of Platelet Activation In Cancer Patientsmentioning

confidence: 99%

Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?

Wojtukiewicz

Hempel²,

Sierko

et al. 2017

Cancer Metastasis Rev

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“…2g). Heat shock proteins, along with histone fragments commonly found in vesicles 12 , were found in MEVs and MEVs Ca . The presence of CD14 in both MEVs and MEVs Ca confirmed their monocytic origin.…”

Section: Resultsmentioning

confidence: 98%

Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles

Halder

Hasan

et al. 2020

Nat Commun

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Extracellular vesicles have an important function in cellular communication. Here, we show that human and mouse monocytes release TGF-β1-transporting vesicles in response to the pathogenic fungus Candida albicans. Soluble β-glucan from C. albicans binds to complement receptor 3 (CR3, also known as CD11b/CD18) on monocytes and induces the release of TGF-β1-transporting vesicles. CR3-dependence is demonstrated using CR3-deficient (CD11b knockout) monocytes generated by CRISPR-CAS9 genome editing and isolated from CR3deficient (CD11b knockout) mice. These vesicles reduce the pro-inflammatory response in human M1-macrophages as well as in whole blood. Binding of the vesicle-transported TGF-β1 to the TGF-β receptor inhibits IL1B transcription via the SMAD7 pathway in whole blood and induces TGFB1 transcription in endothelial cells, which is resolved upon TGF-β1 inhibition. Notably, human complement-opsonized apoptotic bodies induce production of similar TGF-β1transporting vesicles in monocytes, suggesting that the early immune response might be suppressed through this CR3-dependent anti-inflammatory vesicle pathway.

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“…Exosomes are smaller in size, ranging from 40–150 nm, and derived from early endosomes. Apoptotic bodies are larger, measuring 100–5000 nm, and are vesicles that originate from dying cells as they disintegrate [ 4 , 5 ]. EVs are associated with a wide variety of cell types and contain essential macromolecules, including DNA, microRNA (miRNA), messenger RNA (mRNA), proteins, and lipids [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles as Biomarkers in Cancer Immunotherapy

Mathew

Zade

Mezghani

et al. 2020

Cancers

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Extracellular vesicles (EVs), including exosomes and microvesicles, are membrane-bound vesicles secreted by most cell types during both physiologic conditions as well in response to cellular stress. EVs play an important role in intercellular communication and are emerging as key players in tumor immunology. Tumor-derived EVs (TDEs) harbor a diverse array of tumor neoantigens and contain unique molecular signature that is reflective of tumor’s underlying genetic complexity. As such they offer a glimpse into the immune tumor microenvironment (TME) and have the potential to be a novel, minimally invasive biomarker for cancer immunotherapy. Immune checkpoint inhibitors (ICI), such as anti- programmed death-1(PD-1) and its ligand (PD-L1) antibodies, have revolutionized the treatment of a wide variety of solid tumors including head and neck squamous cell carcinoma, urothelial carcinoma, melanoma, non-small cell lung cancer, and others. Typically, an invasive tissue biopsy is required both for histologic diagnosis and next-generation sequencing efforts; the latter have become more widespread in daily clinical practice. There is an unmet need for noninvasive or minimally invasive (e.g., plasma-based) biomarkers both for diagnosis and treatment monitoring. Targeted analysis of EVs in biospecimens, such as plasma and saliva could serve this purpose by potentially obviating the need for tissue sample. In this review, we describe the current challenges of biomarkers in cancer immunotherapy as well as the mechanistic role of TDEs in modulating antitumor immune response

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Not all extracellular vesicles were created equal: clinical implications

Cited by 28 publications

References 26 publications

Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?

Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?

Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles

Extracellular Vesicles as Biomarkers in Cancer Immunotherapy

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