Immune Cell-Derived Extracellular Vesicles – Functions and Therapeutic Applications

Veerman, Rosanne E.; Akpinar, Gözde Güçlüler; Eldh, Maria; Gabrielsson, Susanne

doi:10.1016/j.molmed.2019.02.003

Cited by 200 publications

(150 citation statements)

References 79 publications

Supporting

Mentioning

148

Contrasting

Order By: Relevance

“…Many recent reviews dealing with the potential use of exosomes produced by different cell types as biomarkers of several pathologies and therapies have been published [130][131][132], thus we will center only on some recent publications concerning either preclinical studies with exosomes or potential therapeutic approaches related to exosomes produced by B and T lymphocytes.…”

Section: Some Potential Clinical Applications Of Immune Cells-derivedmentioning

confidence: 99%

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Calvo

Izquierdo

2020

IJMS

View full text Add to dashboard Cite

Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptors (TCR) and B-cell receptors (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular, and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC), the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. As inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this review considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.

show abstract

Section: Some Potential Clinical Applications Of Immune Cells-derivedmentioning

confidence: 99%

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Calvo

Izquierdo

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…EVs function in normal physiological processes, such as reproduction , immune responses (Bruno et al, 2015), neural development and maintenance (Krämer-Albers and Hill, 2016), and metabolism (Thomou et al, 2017). They also have roles in pathological events (Maas et al, 2017;Huang-Doran et al, 2017;Veerman et al, 2019) with much focus on the role of EVs in promoting tumour growth, survival, and metastasis (Becker et al, 2016). These effects involve interactions of tumour cells with each other and surrounding stromal cells (Wendler et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Glutamine Deprivation Regulates the Origin and Function of Cancer Cell Exosomes

Fan

Kroeger

Marie

et al. 2019

Preprint

View full text Add to dashboard Cite

Exosomes are secreted extracellular vesicles (EVs) carrying diverse cargos, which can modulate recipient cell behaviour. They are thought to derive from intraluminal vesicles formed in late endosomal multivesicular bodies (MVBs). An alternate exosome formation mechanism, which is conserved from fly to human, is described here, with exosomes carrying unique cargos, including the GTPase Rab11, generated in Rab11-positive recycling endosomal MVBs. Release of these exosomes from cancer cells is increased by reducing Akt/mechanistic Target of Rapamycin (mTORC1) signalling or depleting the key metabolic substrate glutamine, which diverts membrane flux through recycling endosomes. The resulting vesicles promote tumour cell proliferation and turnover, and modulate blood vessel networks in xenograft mouse models in vivo. Their growth-promoting activity, which is also observed in vitro, is Rab11a-dependent, involves ERK-MAPK-signalling and is inhibited by antibodies against Amphiregulin, an EGFR ligand concentrated on these vesicles. Therefore, glutamine depletion or mTORC1 inhibition stimulates release of Rab11a-exosomes with protumorigenic functions, which we propose promote stress-induced tumour adaptation. KEY WORDSExosome / extracellular vesicle (EV) / mechanistic Target of Rapamycin (mTORC1) / recycling endosome / multivesicular body (MVB) 6 al., 2016). Fluorescent puncta were seen inside YFP-Rab11-positive SC compartments ( Figure 1C), but fewer than with CD63-GFP ( Figure 1B). Moreover, unlike CD63-GFP ( Figure S1B), the Rab11 fusion protein did not traffic to the plasma membrane ( Figure S1C, Movie S2). Sporadic YFP-Rab11-positive puncta were observed in the AG lumen, both in the gene trap line ( Figure S1C) and when YFP-Rab11 was specifically overexpressed in SCs ( Figure S1D). In contrast, a YFP-Rab7 gene trap fusion protein (Dunst et al., 2015) primarily trafficked to acidic LELs ( Figure 1D) and marked very few puncta in the AG lumen. We conclude that Rab11-labelled exosomes are formed at low levels in Rab11 SC compartments and secreted.In searching for other markers of these alternative exosomes, we found that an overexpressed GFP-tagged form of Breathless (Btl; a fly homologue of the human transmembrane FGF receptor), which is normally expressed in SCs ( Figure S1E), trafficked on to ILVs in Rab11compartments ( Figure 1E). Its expression did not affect large non-acidic compartments in SCs and had only a minor effect on acidic compartment number ( Figure S1H-J). In some SCs, Btl-GFP, like YFP-Rab11, was found in the lumen of an LEL, but, unlike CD63-GFP, these markers were rarely, if ever, observed on the LEL limiting membrane ( Figure S2), presumably because they reach LELs by sporadic fusion to Rab11-compartments (Corrigan et al., 2014) and not by endocytic trafficking. As with YFP-Rab11, transmembrane Btl-GFP protein was secreted in puncta into the AG lumen (Figure 2A). We, therefore, conclude that Rab11 and Btl are selective membrane-associated markers for exosomes generated in Rab11compartments of SCs...

show abstract

“…They also play important roles in cardiovascular diseases like acute myocardial infarction and autoimmune diseases such as myasthenia gravis . However, clinical trials show that the use of immune‐cell‐derived exosomes afford limited therapeutic outcomes in living subjects . Thereby, engineering of exosomes to improve their effects is in urgent need.…”

Section: Methodsmentioning

confidence: 99%

Responsive Exosome Nano‐bioconjugates for Synergistic Cancer Therapy

et al. 2019

View full text Add to dashboard Cite

Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano‐bioconjugates for cancer therapy. Azide‐modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne‐modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH‐sensitive linkers. After systemic administration, the nano‐bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic‐imine bonds of the nano‐bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished “don't eat me” signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro‐tumoral M2 to anti‐tumoral M1.

show abstract

Immune Cell-Derived Extracellular Vesicles – Functions and Therapeutic Applications

Cited by 200 publications

References 79 publications

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Glutamine Deprivation Regulates the Origin and Function of Cancer Cell Exosomes

Responsive Exosome Nano‐bioconjugates for Synergistic Cancer Therapy

Contact Info

Product

Resources

About