Translational Potential of RNA Derived From Extracellular Vesicles in Multiple Myeloma

Reale, Antonia; Khong, Tiffany; Mithraprabhu, Sridurga; Spencer, Andrew

doi:10.3389/fonc.2021.718502

Cited by 4 publications

(6 citation statements)

References 89 publications

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“…For example, Khani et al [ 196 ] demonstrated DC-mediated suppression of breast cancer by engineering TEVs with miR-142 and Let7i. We have recently described the utility of EVs engineered with RNA as a strategy to re-activate the immune system against cancers including myeloma [ 197 ]. Although EVs carrying RNAs, including microRNAs, hold great promise as an innovative approach in nanomedicine to fight cancer, their use in clinical practice is still limited [ 198 , 199 , 200 , 201 ].…”

Section: Translational Applications: Targeting Ev-mediated Tumor Immu...mentioning

confidence: 99%

“…As discussed elsewhere [ 6 , 197 ], “a lack of standardised methodologies (e.g., EV purification, quantification, labelling) and data reporting limits inter-study comparisons and the translation of EVs from bench to bedside”. This may explain the discrepancy between the large amount of published research on the role of EVs in the tumor immune microenvironment and the few applications in clinical trial settings.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

“…Ongoing research aims to develop and optimize methodologies for isolation and purification of EVs and EV-subtypes from biological samples and for accurate quantification and content analysis. Our group has demonstrated the critical importance of samples collection and preparation for EV analyses and data interpretation [ 6 , 18 , 197 , 218 ]. Unpublished data inform the utility of critical evaluation of pre-analytical factors for EV-RNA isolation and preparation.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

“…In a recent report, we show for the first time in myeloma that the depletion of human serum albumin (a highly abundant protein in blood) from small EV preparations obtained from blood plasma of myeloma patients, improves the detection of proteins when using mass-spectrometry based proteomics [ 6 , 18 ]. Several methods have been developed for improved EVs’ isolation/purification from different sources and for surface and internal cargo modifications [ 6 , 18 , 223 , 224 , 225 ], with position statements regularly published to provide scientists with protocols for EV isolation/purification, analyses, accurate reporting of pre-analytical variables and methods [ 6 , 197 , 226 ]. As described in this review, circulating EVs play a role as diagnostic markers and as predictive markers of therapeutic response to immunotherapy.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

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Extracellular Vesicles and Their Roles in the Tumor Immune Microenvironment

Reale

Khong

Spencer

2022

JCM

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Tumor cells actively incorporate molecules (e.g., proteins, lipids, RNA) into particles named extracellular vesicles (EVs). Several groups have demonstrated that EVs can be transferred to target (recipient) cells, making EVs an important means of intercellular communication. Indeed, EVs are able to modulate the functions of target cells by reprogramming signaling pathways. In a cancer context, EVs promote the formation of a supportive tumor microenvironment (TME) and (pre)metastatic niches. Recent studies have revealed that immune cells, tumor cells and their secretome, including EVs, promote changes in the TME and immunosuppressive functions of immune cells (e.g., natural killer, dendritic cells, T and B cells, monocytes, macrophages) that allow tumor cells to establish and propagate. Despite the growing knowledge on EVs and on their roles in cancer and as modulators of the immune response/escape, the translation into clinical practice remains in its early stages, hence requiring improved translational research in the EVs field. Here, we comprehensively review the current knowledge and most recent research on the roles of EVs in tumor immune evasion and immunosuppression in both solid tumors and hematological malignancies. We also highlight the clinical utility of EV-mediated immunosuppression targeting and EV-engineering. Importantly, we discuss the controversial role of EVs in cancer biology, current limitations and future perspectives to further the EV knowledge in clinical practice.

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Section: Translational Applications: Targeting Ev-mediated Tumor Immu...mentioning

confidence: 99%

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

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Extracellular Vesicles and Their Roles in the Tumor Immune Microenvironment

Reale

Khong

Spencer

2022

JCM

Self Cite

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“…EVs present similar biomarkers of their cell of origin, and this allows for evaluating them as a useful target for identification and treatment of cancer patients [ 118 ]. Relevantly, EVs defend their cargo including RNAs from destruction in the extracellular space and can be efficaciously isolated from peripheral blood, making them perfect elements for LB [ 119 , 120 ].…”

Section: Liquid Biopsy and Exosomesmentioning

confidence: 99%

Circulating Tumour Cells, Cell Free DNA and Tumour-Educated Platelets as Reliable Prognostic and Management Biomarkers for the Liquid Biopsy in Multiple Myeloma

Allegra

Cancemi

Mirabile

et al. 2022

Cancers

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Liquid biopsy is one of the fastest emerging fields in cancer evaluation. Circulating tumour cells and tumour-originated DNA in plasma have become the new targets for their possible employ in tumour diagnosis, and liquid biopsy can define tumour burden without invasive procedures. Multiple Myeloma, one of the most frequent hematologic tumors, has been the target of therapeutic progresses in the last few years. Bone marrow aspirate is the traditional tool for diagnosis, prognosis, and genetic evaluation in multiple myeloma patients. However, this painful procedure presents a relevant drawback for regular disease examination as it requires an invasive practice. Moreover, new data demonstrated that a sole bone marrow aspirate is incapable of expressing the multifaceted multiple myeloma genetic heterogeneity. In this review, we report the emerging usefulness of the assessment of circulating tumour cells, cell-free DNA, extracellular RNA, cell-free proteins, extracellular vesicles, and tumour-educated platelets to evaluate the changing mutational profile of multiple myeloma, as early markers of disease, reliable predictors of prognosis, and as useful tools to perform less invasive monitoring in multiple myeloma.

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