The immunomodulatory role of tumor‐derived extracellular vesicles in colorectal cancer

Manning, Stephanie; Danielson, Kirsty

doi:10.1111/imcb.12038

Cited by 14 publications

(17 citation statements)

References 56 publications

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“…Specific names have been applied to microvesicles derived from particular cells and tissues, such as oncosomes from tumors (described elsewhere in this issue by Manning and Danielson) and ectosomes from neutrophils. Ectosomes provide a particularly striking example of the multiple ways in which microvesicles affect immunity.…”

Section: Microvesiclesmentioning

confidence: 99%

Dendritic cells and routing cargo into exosomes

2018

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Extracellular vesicles, released from cells, are important for intercellular communication. They are heterogeneous but fall into two broad categories based on origin and function: microvesicles formed by outward budding from the plasma membrane; and exosomes that originate as intraluminal vesicles in multivesicular endosomes that fuse with the plasma membrane to release them. Extracellular vesicles generally and exosomes in particular have powerful effects on specific immune responses, and recent advances highlight their potential therapeutic uses. Dendritic cells (DC) that have internalized antigen release exosomes that express MHC class II molecules loaded with antigenic peptides, co-stimulatory molecules and intact antigen. Depending on the setting, these stimulate CD4 T-cell proliferation either directly or only in the context of accessory antigen naïve DC. Here, we discuss the reasons for this; and review current knowledge about the loading of antigen, class II and other cargo into exosomes released by DC and other professional antigen-presenting cells in the context of advances in exosome biology more generally.

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Section: Microvesiclesmentioning

confidence: 99%

Dendritic cells and routing cargo into exosomes

2018

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“…The authors noted that immune cells and fibroblasts are capable of producing many of these factors at much higher level than tumor cells and pointed out to the role of the stroma in systemic inflammation. Some of these immunomodulatory effects are modulated by exosomes that contain in their cargo a large variety of molecules [92,93] . Exosomes secreted by tumors contain IL-8, CCL2, CCL3, CCL4, CCL5, CCL20 and TGF-β [93] .…”

Section: The Systemic Inflammation Networkmentioning

confidence: 99%

The systemic hallmarks of cancer

Paul¹

2020

JCMT

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Cancer is not just a lump of cells that divide, invade, and spread randomly, but rather a multi-layered precisely tuned process that requires the participation of the whole organism. There is an urgent need to zoom-out from the cellular and the local stromal view and broaden our perspective by including the whole organism level. Geographically separated cancer tissues communicate between themselves, forming a system that interacts with the rest of the organism through cancer induced systemic pathogenic networks. In the present paper, I introduce six systemic hallmarks of cancer that emerge as a result of these interactions. I also describe several potential therapeutic approaches that can be developed using the cancer system concept. Overall, I argue that the tumoricentric paradigm should be replaced with a broader approach that brings into focus the "cancerized" organism.

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“…Recently, extracellular vesicles have come into focus as functional mediators of carcinogenesis and metastasis. 9 Extracellular vesicles are nanosized, membrane-encapsulated information carriers secreted by all living cells. 10 Consequently, they have been detected in various body fluids including serum, plasma, urine, and cerebrospinal fluid, where they transport macromolecules such as proteins, cytokines, messenger RNA (mRNA), and microRNA.…”

Section: Editor's Perspectivementioning

confidence: 99%

Propofol and Sevoflurane Differentially Impact MicroRNAs in Circulating Extracellular Vesicles during Colorectal Cancer Resection

et al. 2020

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Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Extracellular vesicles and their microRNA cargo are crucial facilitators of malignant cell communication and could mediate effects of anesthetics on tumor biology during cancer resection. The authors performed a proof-of-concept study to demonstrate that propofol and sevoflurane have differential effects on vesicle-associated microRNAs that influence signaling pathways involved in tumor progression and metastasis. Methods Circulating vesicles were investigated in a prospective, matched-case pilot study in two cohorts of colorectal cancer patients receiving either propofol (n = 8) or sevoflurane (n = 9), matched for tumor stage and location. Serum was sampled before anesthesia and after tumor resection. Vesicular microRNA profiles were analyzed by next generation sequencing and confirmed by real-time polymerase chain reaction. Next, we assessed perioperative changes in microRNA expression induced by either anesthetic and compared their biologic effects on tumor-relevant pathways. Additionally, vesicles from pre- and postoperative sera were biologic characterized. Results Postoperative microRNA profiles were shifted in both groups with overlap in the perioperative response. A total of 64 (48 up, range of log2 fold change 1.07 to 3.76; 16 down, −1.00 to −1.55) and 33 (32 up, 1.02 to 2.98; 1 down, −1.36) microRNAs were significantly regulated (adjusted P value less than 0.05) by propofol and sevoflurane, respectively. Thirty-six (propofol) and five (sevoflurane) microRNAs were specifically responsive to either anesthetic agent. In silico target analyses of microRNA expression patterns indicated an inhibitory effect of propofol on crucial carcinoma-related pathways such as proliferation (z-score, −1.73) and migration (z-score, −1.97), as well as enhanced apoptosis (z-score, 1.19). While size distribution and protein markers of circulating vesicles were not affected by anesthesia, their concentration was reduced after surgery using both anesthetic procedures. Conclusions This proof-of-concept study provides preliminary evidence that anesthetic agents have specific effects on microRNA profiles in circulating vesicles. These findings could form the basis for larger and mechanistically oriented outcome studies in cancer patients.

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The immunomodulatory role of tumor‐derived extracellular vesicles in colorectal cancer

Cited by 14 publications

References 56 publications

Dendritic cells and routing cargo into exosomes

Dendritic cells and routing cargo into exosomes

The systemic hallmarks of cancer

Propofol and Sevoflurane Differentially Impact MicroRNAs in Circulating Extracellular Vesicles during Colorectal Cancer Resection

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