Landscape of extracellular vesicles in the tumour microenvironment: Interactions with stromal cells and with non-cell components, and impacts on metabolic reprogramming, horizontal transfer of neoplastic traits, and the emergence of therapeutic resistance

Zhang, Daniel Xin; Vu, Luyen Tien; Ismail, Nur Nadiah; Le, Minh Tn; Grimson, Andrew

doi:10.1016/j.semcancer.2021.01.007

Cited by 37 publications

(34 citation statements)

References 334 publications

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“…This may represent a druggable target to enhance immune-mediated tumor response, and there are currently ongoing trials evaluating this strategy [ 91 , 92 ]. Lastly, tumor-derived extracellular vesicles (EVs), which mediate cell-to-cell interactions, have been shown to express PD-L1 and may contribute towards T cell suppression [ 93 ]. The impact of EVs has been shown to be relevant in HCC, as EV-derived molecules such as ubiquitin-like with PHD and RING finger domain (UHFR1) induce NK cell dysfunction in HCC patients [ 94 ].…”

Section: Future Directionsmentioning

confidence: 99%

Immunotherapy Updates in Advanced Hepatocellular Carcinoma

Singh

Beechinor

Huynh

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. HCC tumor development and treatment resistance are impacted by changes in the microenvironment of the hepatic immune system. Immunotherapy has the potential to improve response rates by overcoming immune tolerance mechanisms and strengthening anti-tumor activity in the tumor microenvironment. In this review, we characterize the impact of immunotherapy on outcomes of advanced HCC, as well as the active clinical trials evaluating novel combination immunotherapy strategies. In particular, we discuss the efficacy of atezolizumab and bevacizumab as demonstrated in the IMbrave150 study, which created a new standard of care for the front-line treatment of advanced HCC. However, there are multiple ongoing trials that may present additional front-line treatment options depending on their efficacy/toxicity results. Furthermore, the preliminary data on the application of chimeric antigen receptor (CAR-T) cell therapy for treatment of HCC suggests this may be a promising option for the future of advanced HCC treatment.

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Section: Future Directionsmentioning

confidence: 99%

Immunotherapy Updates in Advanced Hepatocellular Carcinoma

Singh

Beechinor

Huynh

et al. 2021

Cancers

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“…Second, GFP absorbance can serve as a proxy for cell number, which would offer additional information to the MTS readout. MTS typically evaluates cell proliferation by assuming stable mitochondrial activity ( 88 ), and we can imagine that EV-induced metabolic changes in recipient cells ( 89 – 91 ) could alter that assumption and affect the assay’s reproducibility. Third, GFP absorbance of this fluorescent cell line offers the ability to compare across experiments; in our hands the absorbance of plated HS5-GFP cells for the buffer control wells at time points was comparable across experiments (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Optimizing extracellular vesicles’ isolation from chronic lymphocytic leukemia patient plasma and cell line supernatant

Elgamal¹,

Cocucci

Sass³

et al. 2021

JCI Insight

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“…EVs are actively involved in the formation and progression of multiple cancers, and also function in the development of non‐cancer diseases, such as neurodegenerative disease, metabolic diseases, and intestinal ischemia/reperfusion injury (Figure 4 ). They have been found to transfer metabolites, facilitate intercellular communication, and influence the formation of aggregates of abnormally folded or unfolded proteins (Hurwitz et al., 2018 , Levy, 2017 , Matarredona & Pastor, 2019 , Muraoka et al., 2020 , Soria et al., 2017 , Zhang et al., 2021 ). Recently, Ti‐EVs have attracted significant interest in studies on various diseases owing to their favourable properties.…”

Section: Ti‐evs In Non‐cancer Diseasesmentioning

confidence: 99%

Tissue‐derived extracellular vesicles in cancers and non‐cancer diseases: Present and future

Man

Gao

et al. 2021

J of Extracellular Vesicle

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Extracellular vesicles (EVs) are lipid‐bilayer membrane structures secreted by most cell types. EVs act as messengers via the horizontal transfer of lipids, proteins, and nucleic acids, and influence various pathophysiological processes in both parent and recipient cells. Compared to EVs obtained from body fluids or cell culture supernatants, EVs isolated directly from tissues possess a number of advantages, including tissue specificity, accurate reflection of tissue microenvironment, etc., thus, attention should be paid to tissue‐derived EVs (Ti‐EVs). Ti‐EVs are present in the interstitium of tissues and play pivotal roles in intercellular communication. Moreover, Ti‐EVs provide an excellent snapshot of interactions among various cell types with a common histological background. Thus, Ti‐EVs may be used to gain insights into the development and progression of diseases. To date, extensive investigations have focused on the role of body fluid‐derived EVs or cell culture‐derived EVs; however, the number of studies on Ti‐EVs remains insufficient. Herein, we summarize the latest advances in Ti‐EVs for cancers and non‐cancer diseases. We propose the future application of Ti‐EVs in basic research and clinical practice. Workflows for Ti‐EV isolation and characterization between cancers and non‐cancer diseases are reviewed and compared. Moreover, we discuss current issues associated with Ti‐EVs and provide potential directions.

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Landscape of extracellular vesicles in the tumour microenvironment: Interactions with stromal cells and with non-cell components, and impacts on metabolic reprogramming, horizontal transfer of neoplastic traits, and the emergence of therapeutic resistance

Cited by 37 publications

References 334 publications

Immunotherapy Updates in Advanced Hepatocellular Carcinoma

Immunotherapy Updates in Advanced Hepatocellular Carcinoma

Optimizing extracellular vesicles’ isolation from chronic lymphocytic leukemia patient plasma and cell line supernatant

Tissue‐derived extracellular vesicles in cancers and non‐cancer diseases: Present and future

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