The Crosstalk between Cancer Stem Cells and Microenvironment Is Critical for Solid Tumor Progression: The Significant Contribution of Extracellular Vesicles

Leone, Alessandra; Budillon, Alfredo

doi:10.1155/2018/6392198

Cited by 32 publications

(22 citation statements)

References 115 publications

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“…The TME was shown to be immunosuppressive, which is a key reason why most cancer immune therapies often display limited clinical efficacy [23]. IL-17A is an inflammatory cytokine secreted by different cell types, including CD4 + T helper cells (Th17), CD8 + T cells, and γδT cells [24,25].…”

Section: Introductionmentioning

confidence: 99%

Th17 cells inhibit CD8+ T cell migration by systematically downregulating CXCR3 expression via IL-17A/STAT3 in advanced-stage colorectal cancer patients

Wang

Lian

et al. 2020

J Hematol Oncol

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Background: CD8 + T cell trafficking to the tumor site is essential for effective colorectal cancer (CRC) immunotherapy. However, the mechanism underlying CD8 + T cell infiltration in colorectal tumor tissues is not fully understood. In the present study, we investigated CD8 + T cell infiltration in CRC tissues and the role of chemokinechemokine receptor signaling in regulation of T cell recruitment. Methods: We screened chemokines and cytokines in healthy donor and CRC tissues from early-and advancedstage patients using multiplex assays and PCR screening. We also utilized transcription factor activation profiling arrays and established a xenograft mouse model. Results: Compared with tumor tissues of early-stage CRC patients, CD8 + T cell density was lower in advanced-stage tumor tissues. PCR screening showed that CXCL10 levels were significantly increased in advanced-stage tumor tissues. CXCR3 (the receptor of CXCL10) expression on CD8 + T cells was lower in the peripheral blood of advancedstage patients. The migratory ability of CD8 + T cells to CXCL10 depended on CXCR3 expression. Multiplex arrays showed that IL-17A was increased in advanced-stage patient sera, which markedly downregulated CXCR3 expression via activating STAT3 signaling and reduced CD8 + T cell migration. Similar results were found after CD8 + T cells were treated with Th17 cell supernatant. Adding anti-IL-17A or the STAT3 inhibitor, Stattic, rescued these effects in vitro and in vivo. Moreover, survival analysis showed that patients with low CD8 and CXCR3 expression and high IL-17A levels had significantly worse prognosis. Conclusions: CD8 + T cell infiltration in advanced-stage tumor was systematically inhibited by Th17 cells via IL-17A/ STAT3/CXCR3 axis. Our findings indicate that the T cell infiltration in the tumor microenvironment may be improved by inhibiting STAT3 signaling.

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Section: Introductionmentioning

confidence: 99%

Th17 cells inhibit CD8+ T cell migration by systematically downregulating CXCR3 expression via IL-17A/STAT3 in advanced-stage colorectal cancer patients

Wang

Lian

et al. 2020

J Hematol Oncol

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“…MAGEA proteins are good immunogens which evoke a strong CTL (cytotoxic T lymphocyte) response in patients [1]. The uptake of tumor derived EVs by immune cells may have functional consequences on the immune microenvironment, which can result in either escaping the immune response or in activating immune suppression [35]. MAGEA-positive EVs may have a role in this process as microvesicles are known to modulate the immune response [36].…”

Section: Discussionmentioning

confidence: 99%

Cancer-testis antigens MAGEA proteins are incorporated into extracellular vesicles released by cells

et al. 2019

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Melanoma-associated antigen A (MAGEA) family proteins represent a class of tumor antigens that are expressed in a variety of malignant tumors, but their expression in normal tissues is restricted to germ cells. MAGEA family consists of eleven proteins that are highly conserved sharing the common MAGE homology domain (MHD). In the current study, we show that MAGEA4 and MAGEA10 proteins are incorporated into extracellular vesicles released by mouse fibroblast and human osteosarcoma U2OS cells and are expressed, at least partly, on the surface of released EVs. The C-terminal part of the protein containing MHD domain is required for this activity. Expression of MAGEA proteins induced the budding of cells and formation of extracellular vesicles with 150 to 1500 nm in diameter. Our data suggest that the release of MAGEA-positive EVs is at least to some extent induced by the expression of MAGEA proteins itself. This may be one of the mechanisms of MAGEA proteins to induce cancer formation and progression.

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“…67 Similarly, TEXs have been demonstrated to induce malignant transformation in prostate cancer. 68 Furthermore, the heterogeneous tumor cell mass contains a small subpopulation so-called cancer stem cells (CSCs) with self-renewal and differentiation potential, considered to be the main cause of tumor recurrence. [69][70][71] One of the prominent features of CSCs is their plasticity and dynamic equilibrium, where CSC-TEXs play a crucial role.…”

Section: Texs In Tumor Cell and Stroma Modulationmentioning

confidence: 99%

“… 72 - 74 Thus, CSC-TEXs can remodel the tumor niche through influencing resident tumor cells as well as the tumor microenvironment including fibroblasts and immune cells, which leads to local tumor progression. 68 In prostate cancer, differential microRNA patterns were observed in bulk cell-TEXs and CSC-TEXs. The CSC-TEXs miRNA profile suggested an involvement in angiogenesis, proliferation, and pre-metastatic niche formation.…”

Section: Texs In Tumor Cell and Stroma Modulationmentioning

confidence: 99%

Tumor-derived exosomes: the next generation of promising cell-free vaccines in cancer immunotherapy

et al. 2020

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Identification of immunogenic tumor antigens that are efficiently processed and delivered by dendritic cells to prime the immune system and to induce an appropriate immune response is a research hotspot in the field of cancer vaccine development. High biosafety is an additional demand. Tumor-derived exosomes (TEXs) are nanosized lipid bilayer encapsulated vesicles that shuttle bioactive information to the tumor microenvironment facilitating tumor progression. However, accumulating evidence points toward the capacity of TEXs to efficiently stimulate immune responses against tumors provided they are appropriately administered. After briefly describing the function of exosomes in cancer biology and their communication with immune cells, we summarize in this review in vitro and preclinical studies eliciting the potency of TEXs in inducing effective anti-tumor responses and recently modified strategies further improving TEX-vaccination efficacy. We interpret the available data as TEXs becoming a lead in cancer vaccination based on tumor antigen-selective high immunogenicity.

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The Crosstalk between Cancer Stem Cells and Microenvironment Is Critical for Solid Tumor Progression: The Significant Contribution of Extracellular Vesicles

Cited by 32 publications

References 115 publications

Th17 cells inhibit CD8+ T cell migration by systematically downregulating CXCR3 expression via IL-17A/STAT3 in advanced-stage colorectal cancer patients

Th17 cells inhibit CD8+ T cell migration by systematically downregulating CXCR3 expression via IL-17A/STAT3 in advanced-stage colorectal cancer patients

Cancer-testis antigens MAGEA proteins are incorporated into extracellular vesicles released by cells

Tumor-derived exosomes: the next generation of promising cell-free vaccines in cancer immunotherapy

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