Extracellular vesicles: masters of intercellular communication and potential clinical interventions

Pitt, Jonathan M.; Kroemer, Guido; Zitvogel, Laurence

doi:10.1172/jci87316

Cited by 425 publications

(334 citation statements)

References 73 publications

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“…2,4 Several studies describe the involvement of exosomes in the modulation of both innate and adaptive immune response through different mechanisms. 1,3,46 As for NK cells, the immunomodulatory role of exosomes appears to be multi-faceted and dependent on the identity of both the exosomes-associated cargo end exosome releasing cells.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In this context, a fast developing field is that focusing on how exosomes released by cancer cells in the tumor microenvironment are uptaken by different immune cell types, thereby modulating antitumor immune response and affecting tumor progression. 3,4 Natural killer (NK) cells are innate immune effectors that play a pivotal role in tumor immunosurveillance by exerting direct cytotoxic effects as well as producing a variety of cytokines. NK cell activation is tightly regulated by a fine balance between activating and inhibitory signals.…”

Section: Introductionmentioning

confidence: 99%

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Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

et al. 2017

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Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM. Our findings show that melphalan, a genotoxic agent used in MM therapy, significantly induces an increased exosome release from MM cells. MM cell-derived exosomes are capable of stimulating IFNg production, but not the cytotoxic activity of NK cells through a mechanism based on the activation of NF-kB pathway in a TLR2/ HSP70-dependent manner. Interestingly, HSP70C exosomes are primarily found in the bone marrow (BM) of MM patients suggesting that they might have a crucial immunomodulatory action in the tumor microenvironment. We also provide evidence that the CD56 high NK cell subset is more responsive to exosome-induced IFNg production mediated by TLR2 engagement. All together, these findings suggest a novel mechanism of synergism between chemotherapy and antitumor innate immune responses based on the drug-promotion of nanovesicles exposing DAMPs for innate receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

et al. 2017

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“…Some MT-based clinical treatments, as it is the case of deep tissue or cross-friction massage, utilize high force to induce transient local inflammation with the final goal of promoting repair and regeneration [129]. Although a benefit from this approach cannot be completely discarded at this point, a preferential exploration of medium load based MT protocols is recommended for the treatment of FM and CFS/ME with the intention of minimizing patient discomfort while providing health improvements.…”

Section: Future Directionsmentioning

confidence: 99%

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

Espejo¹,

García-Escudero²,

Oltra³

2018

Preprint

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Abstract:Application of protocols without parameter standardization and rigorous controls has led manual therapy (MT) and other physiotherapy approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way this can be achieved is by studying gene expression and additional physiological changes that associate to particular, parameter-controlled, treatments in animal models and translating this knowledge to properly design objective, quantitatively-monitored clinical trials. Here, we propose a Molecular Physiotherapy Approach (MPTA), requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports of MT that historically attribute benefits to these treatments. The review focuses in the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and CFS/ME. The systemic effect associated to mechanical-load responses is considered of particular relevance as it suggests that defined, low-pain areas could be selected for treatments with overall benefits, an aspect that might result essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to treat FM and CFS/ME.

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“…3,4,5,6,7 Algunas proteínas altamente enriquecidas en exosomas son empleadas como marcadores para identificar a estas vesículas, algunos ejemplos incluyen a Hsp70 o las tetraspaninas CD9, CD63 y CD81. Las células emplean a estas nanovesículas como medio de comunicación con células adyacentes o muy distantes entre sí; las moléculas presentes en la superficie de las EV les permiten el reconocimiento de células blanco.…”

Section: Abreviaturas Y Siglasunclassified

Los exosomas de las células presentadoras de antígeno y su papel en la regulación de las respuestas inmunológicas

Maravillas‐Montero

Martínez-Cortés

2017

RAM

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Este artículo debe citarse como: Maravillas-Montero JL, Martínez-Cortés I. Los exosomas de las células presentadoras de antígeno y su papel en la regulación de las respuestas inmunológicas. Rev Alerg Mex. 2017;64(4) AbstractCells release several biomolecules to the extracellular environment using them as a communication alternative with neighbor cells. Besides these molecules, cells also release more complex elements, like vesicles; structures composed of a lipidic bilayer with transmembrane proteins that protect a hydrophilic content. Exosomes are a small subtype of vesicles (30-150 nm), produced by many cell types, such as tumor cells, neurons, epithelial cells and immune cells. Included in this last group, antigen presenting cells produce exosomes that contain different types of molecules depending on their activation and/or maturation state. In recent years there has been an exponential interest in exosomes due to the recent evidences that show the immunomodulatory properties of these vesicles and therefore, their great potential in diagnostic approaches and development of therapies for different inflammation-associated pathologies.

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Extracellular vesicles: masters of intercellular communication and potential clinical interventions

Cited by 425 publications

References 73 publications

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

Los exosomas de las células presentadoras de antígeno y su papel en la regulación de las respuestas inmunológicas

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