Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

Raimondo, Stefania; Pucci, Marzia; Alessandro, Riccardo; Fontana, Simona

doi:10.3390/ijms21072286

Cited by 59 publications

(46 citation statements)

References 152 publications

(184 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since Tregs suppress the activity of effector T-cells, hypoxia tends to create an immunosuppressive TME. Moreover, HIF1-α works as a direct inducer of PD-L1 (Programmed Death-Ligand 1) expression in cancer cells, macrophages, dendritic cells, and MDSCs, resulting in further effector T-cell inhibition and enhancing tumor immune escape [ 71 , 72 ]. In contrast to previous findings, it has been reported that HIF1-α stimulates immune activation by positively modulating the function of cytotoxic T-cells and contributing to NK cell activation [ 73 , 74 ].…”

Section: Dual Role Of Hypoxia In Inflammation and Immune System Rementioning

confidence: 99%

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Corrado

Fontana

2020

IJMS

Self Cite

134

View full text Add to dashboard Cite

The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both acute and chronic human diseases related to the heart, lung, liver, and kidney.

show abstract

Section: Dual Role Of Hypoxia In Inflammation and Immune System Rementioning

confidence: 99%

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Corrado

Fontana

2020

IJMS

Self Cite

134

View full text Add to dashboard Cite

show abstract

“…sEV have gained interest due to their essential role in “normal” intercellular signaling and communication, which impact the physiological balance and homeostasis as well as disease progression. [ 1 , 6 , 32 , 33 , 34 , 35 , 36 ]. Importantly, sEV can modulate the phenotype/functions of recipient cells, even those located in distant organs [ 2 , 3 , 35 , 36 , 37 , 38 ].…”

Section: General Characteristics Of Sevmentioning

confidence: 99%

“…Immunosuppressive activity of MTEX depends on their ligands that engage the T cell receptor (TCR) and IL-2 receptor (IL-2R). Recent studies showed that MTEX inhibited signaling and proliferation of activated primary CD8 + T cells, inducing their apoptosis [ 25 , 32 , 90 ]. Furthermore, MTEX significantly promoted conversion of CD4(+) T cells to CD4(+)CD25(+)FOXP3(+) T regulatory cells (Treg) enhancing their suppressor functions [ 25 ].…”

Section: Biological Activity Of Mtexmentioning

confidence: 99%

Signaling of Tumor-Derived sEV Impacts Melanoma Progression

Zebrowska

Widłak

Whiteside

et al. 2020

IJMS

View full text Add to dashboard Cite

Small extracellular vesicles (sEV or exosomes) are nanovesicles (30–150 nm) released both in vivo and in vitro by most cell types. Tumor cells produce sEV called TEX and disperse them throughout all body fluids. TEX contain a cargo of proteins, lipids, and RNA that is similar but not identical to that of the “parent” producer cell (i.e., the cargo of exosomes released by melanoma cells is similar but not identical to exosomes released by melanocytes), possibly due to selective endosomal packaging. TEX and their role in cancer biology have been intensively investigated largely due to the possibility that TEX might serve as key component of a “liquid tumor biopsy.” TEX are also involved in the crosstalk between cancer and immune cells and play a key role in the suppression of anti-tumor immune responses, thus contributing to the tumor progression. Most of the available information about the TEX molecular composition and functions has been gained using sEV isolated from supernatants of cancer cell lines. However, newer data linking plasma levels of TEX with cancer progression have focused attention on TEX in the patients’ peripheral circulation as potential biomarkers of cancer diagnosis, development, activity, and response to therapy. Here, we consider the molecular cargo and functions of TEX as potential biomarkers of one of the most fatal malignancies—melanoma. Studies of TEX in plasma of patients with melanoma offer the possibility of an in-depth understanding of the melanoma biology and response to immune therapies. This review features melanoma cell-derived exosomes (MTEX) with special emphasis on exosome-mediated signaling between melanoma cells and the host immune system.

show abstract

“…The inexplicable nature of exosomes has raised concern about their role in the invasion and metastasis of cancer cells, encompassing epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune regulation [ 12 ]. Thus, instead of reviewing the isolated impact of exosomes, e.g., evasion of immune surveillance [ 13 ] for cancer progression, we have tried to encompass exosome-mediated propagation of oncogenic signaling, epigenetic regulation, modulation of tumor microenvironment (TME) and immune escape, EMT, angiogenesis, metastasis and drug resistance. Considering the clinical applications, the exosomes serve as potent diagnostic and prognostic biomarkers because of their bioavailability, low toxicity and differentiated surface markers [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Sinha

Roy

Saha

et al. 2021

Cancers

View full text Add to dashboard Cite

Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.

show abstract

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

Cited by 59 publications

References 152 publications

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Signaling of Tumor-Derived sEV Impacts Melanoma Progression

Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Contact Info

Product

Resources

About