Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages

Popēna, Ineta; Ābols, Artūrs; Saulīte, Līga; Pleiko, Kārlis; Zandberga, Elīna; Jēkabsons, Kaspars; Endzeliņš, Edgars; Llorente, Alicia; Linē, Aija; Riekstiņa, Una

doi:10.1186/s12964-018-0229-y

Cited by 76 publications

(60 citation statements)

References 38 publications

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“…No wonder that Csf2-dependent BMM secreted more proinflammatory cytokines after exposure to LPS. In our study, M1 macrophages polarization was induced with THP-1 cells by incubation with LPS and IFN-γ according to routine protocol ( 44 , 45 ). After stimuli macrophage expressed the typical M1 makers, and Csf2 induced the transformation from M1 to M2.…”

Section: Discussionmentioning

confidence: 99%

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Zhai

Zhang

et al. 2020

Front. Immunol.

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Sepsis is a systemic inflammatory state that occurs in response to infection and significantly increases mortality in combination with acute kidney injury (AKI). Macrophages accumulate in the kidney after injury and undergo a transition from a proinflammatory (M1) phenotype to an alternatively activated (M2) phenotype that is required for normal repair. However, the specific signals that regulate the transition from the M1 to M2 phenotype in vivo are unknown. Here, we found an unexpected role of Colony stimulating factor 2 (Csf2) in controlling macrophage transition in vitro and in a mouse model of sepsis induced by cecal ligation and puncture (CLP). We first co-cultured human M1 macrophages with HK-2 cells and characterized cytokine/chemokine profiles via Luminex. Of the cytokines and chemokines that were overexpressed in medium from M1 macrophages cocultured with human kidney-2 (HK-2) cells compared with that from M1 macrophages cultured alone, Csf2 and IL6 showed the greatest increases. Csf2 was exclusively secreted by HK-2 cells but not by M1 macrophages. Furthermore, recombinant human Csf2 protein promoted transition of M1 macrophages to the M2 phenotype in a dose and time-dependent manner. The apoptosis and reactive oxygen species (ROS) release induced by M1 macrophages in HK-2 cells was attenuated after exposure to exogenous Csf2. In addition, the switch from the proinflammatory M1 phenotype to the M2 phenotype occurred via the p-Stat5 pathway, which was activated by Csf2. Importantly, we found that intraperitoneal injection of a Csf2-neutralizing antibody after CLP aggravated kidney injury and suppressed tubular proliferation, subsequently decreasing survival. However, administration of recombinant mouse Csf2 protein could rescue mice with sepsis. Together, our results indicate that Csf2 plays critical roles in regulating macrophage transition via activation of p-STAT5. These data form a foundation upon which new therapeutic strategies can be designed to improve the therapeutic efficacy of cytokine-based treatments for sepsis-induced AKI.

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Section: Discussionmentioning

confidence: 99%

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Zhai

Zhang

et al. 2020

Front. Immunol.

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“…Growing evidences suggested a role of TEV in regulating the polarization of macrophages [ 91 ]. Thus, EV produced by colorectal cancer and melanoma cells were reported to induce mixed M1 and M2 polarization and cytokine production [ 74 , 92 , 93 ]. Breast cancer-derived EV have been demonstrated to induce an IL-6-mediated pathway via gp130/STAT3 signaling, leading to TAM polarization [ 94 ].…”

Section: Ev In Crosstalk Between Tumor Cells and Macrophagesmentioning

confidence: 99%

Myeloid Cell Modulation by Tumor-Derived Extracellular Vesicles

Arkhypov

Lasser

Petrova

et al. 2020

IJMS

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Extracellular vesicles (EV) can carry proteins, RNA and DNA, thus serving as communication tools between cells. Tumor cells secrete EV, which can be taken up by surrounding cells in the tumor microenvironment as well as by cells in distant organs. Tumor-derived EV (TEV) contain factors induced by tumor-associated hypoxia such as heat shock proteins or a variety of microRNA (miRNA). The interaction of TEV with tumor and host cells can promote cancer angiogenesis, invasion and metastasis. Myeloid cells are widely presented in tissues, comprise the majority of immune cells and play an essential role in immune reactions and tissue remodeling. However, in cancer, the differentiation of myeloid cells and their functions are impaired, resulting in tumor promotion. Such alterations are due to chronic inflammatory conditions associated with cancer and are mediated by the tumor secretome, including TEV. A high capacity of myeloid cells to clear EV from circulation put them in the central position in EV-mediated formation of pre-metastatic niches. The exposure of myeloid cells to TEV could trigger numerous signaling pathways. Progenitors of myeloid cells alter their differentiation upon the contact with TEV, resulting in the generation of myeloid-derived suppressor cells (MDSC), inhibiting anti-tumor function of T and natural killer (NK) cells and promoting thereby tumor progression. Furthermore, TEV can augment MDSC immunosuppressive capacity. Different subsets of mature myeloid cells such as monocytes, macrophages, dendritic cells (DC) and granulocytes take up TEV and acquire a protumorigenic phenotype. However, the delivery of tumor antigens to DC by TEV was shown to enhance their immunostimulatory capacity. The present review will discuss a diverse and complex EV-mediated crosstalk between tumor and myeloid cells in the context of the tumor type, TEV-associated cargo molecules and type of recipient cells.

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“…Conversely, it was discussed that miR-145 positive EVs derived from CRC (CRC-EVs) were most likely polarising surrounding macrophages into the M2 phenotype and thus supporting tumour enlargement [ 115 ]. It was also suggested that primary CRC-EVs could adjust the secretory pattern in monocytes and macrophages to proceed to an advanced cancer stage, whereas metastatic CRC-EVs, associated with high mortality, were associated with an increased serum level of IL-10 [ 116 ]. Similarly, small EVs from HCC cells (HCC-sEVs) transfer high levels of lncRNA TUC339 towards neighbouring cells for tumour-immune crosstalk, and subsequently polarise macrophages to an M2 phenotype, which is associated with dropped cytokine concentrations and impaired phagocytosis [ 117 ].…”

Section: Evs In Gastrointestinal (Gi) and Liver Cancer Managementmentioning

confidence: 99%

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

Słomka

Mocan

Wang

et al. 2020

Cancers

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For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour’s favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

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Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages

Cited by 76 publications

References 38 publications

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Myeloid Cell Modulation by Tumor-Derived Extracellular Vesicles

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

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