Tumor-Related Exosomes Contribute to Tumor-Promoting Microenvironment: An Immunological Perspective

Chen, Wuzhen; Jiang, Jingxin; Xia, Wenjie; Huang, Jian

doi:10.1155/2017/1073947

Cited by 83 publications

(67 citation statements)

References 97 publications

(134 reference statements)

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“…Moreover, ER stress stimulates the release of extracellular vesicles and exosomes which contain, e.g., danger-associated molecular patterns (DAMP) and noncoding RNAs [134,135]. Exosomes augment the expansion of MDSCs and Tregs and thus they are crucial enhancers of immune suppression in tumors [136]. In addition, tumorderived exosomes can suppress the functions of effector immune cells, e.g.…”

Section: Er Stress Augments the Immunosuppressive Phenotype Of Immunementioning

confidence: 99%

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ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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The endoplasmic reticulum (ER) contains stress sensors which recognize the accumulation of unfolded proteins within the lumen of ER, and subsequently these transducers stimulate the unfolded protein response (UPR). The ER sensors include the IRE1, PERK, and ATF6 transducers which activate the UPR in an attempt to restore the quality of protein folding and thus maintain cellular homeostasis. If there is excessive stress, UPR signaling generates alarmins, e.g., chemokines and cytokines, which activate not only tissue-resident immune cells but also recruit myeloid and lymphoid cells into the affected tissues. ER stress is a crucial inducer of inflammation in many pathological conditions. A chronic low-grade inflammation and cellular senescence have been associated with the aging process and many age-related diseases, such as Alzheimer's disease. Currently, it is known that immune cells can exhibit great plasticity, i.e., they are able to display both pro-inflammatory and anti-inflammatory phenotypes in a context-dependent manner. The microenvironment encountered in chronic inflammatory conditions triggers a compensatory immunosuppression which defends tissues from excessive inflammation. Recent studies have revealed that chronic ER stress augments the suppressive phenotypes of immune cells, e.g., in tumors and other inflammatory disorders. The activation of immunosuppressive network, including myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), has been involved in the aging process and Alzheimer's disease. We will examine in detail whether the ER stress-related changes found in aging tissues and Alzheimer's disease are associated with the activation of immunosuppressive network, as has been observed in tumors and many chronic inflammatory diseases.

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Section: Er Stress Augments the Immunosuppressive Phenotype Of Immunementioning

confidence: 99%

“…dendritic and NK cells. It seems that noncoding miRNAs are essential in the generation of immune suppression in tumors [135,136]. Interestingly, exosomes might have an important role in Alzheimer's pathology [137].…”

Section: Er Stress Augments the Immunosuppressive Phenotype Of Immunementioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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“…The immunomodulation induced by exosomes are complex and dynamic . They can promote immunity via presenting tumor antigens and immune‐activators like heat shock proteins, shaping inflammatory microenvironment and suppressing tumor growth . However, tumor associated exosomes tend to mediate immune suppression to promote tumor progression, both systematically and regionally.…”

Section: Exosomes In Sequential Processes Of Tumor Metastasismentioning

confidence: 99%

“…45 They can promote immunity via presenting tumor antigens and immune-activators like heat shock proteins, shaping inflammatory microenvironment and suppressing tumor growth. [46][47][48] However, tumor associated exosomes tend to mediate immune suppression to promote tumor progression, both systematically and regionally. 49 Systematically, cancer cells are able to inhibit antitumor functions of host immune system via exosome-induced inflammatory signaling pathways.…”

Section: Exosomes In Sequential Processes Of Tumor Metastasismentioning

confidence: 99%

Exosomes play roles in sequential processes of tumor metastasis

Chen

et al. 2018

Intl Journal of Cancer

129

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Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.

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“…Tumor-derivedextracellularvesiclesactivateprimary monocytes the function of dendritic cells [9], and inhibit differentiation of myeloid cells [10]. In essence, TEVs constitute a relevant part of the bidirectional communication between tumor cells and cells in the tumor microenvironment [11,12 for review].…”

Section: Original Researchmentioning

confidence: 99%

Tumor‐derived extracellular vesicles activate primary monocytes

et al. 2018

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Tumor cells educate immune effector cells in their vicinity by releasing factors that manipulate their phenotype and function. In fact, the thus generated immunosuppressive tumor microenvironment constitutes an integral part and a hallmark of solid tumors and contributes significantly to tumor development and immune escape. It has long been thought that soluble factors like prostaglandin E2 and TGF‐β are the main mediators of these effects. But tumor cells also constantly release large number of extracellular vesicles (EVs), which are important conveyors of immune responses. We show here that tumor‐derived EVs interact with primary monocytes and induce an activated phenotype, which is also observed in tumor‐associated macrophages. Thus, both tumor‐derived EVs and soluble factors together collaborate to form the immunosuppressive milieu of the tumor environment.

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Tumor-Related Exosomes Contribute to Tumor-Promoting Microenvironment: An Immunological Perspective

Cited by 83 publications

References 97 publications

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

Exosomes play roles in sequential processes of tumor metastasis

Tumor‐derived extracellular vesicles activate primary monocytes

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