scholarly journals Tumor extracellular vesicles are required for tumor-associated macrophage programming

2018 ◽  
Author(s):  
Daniel C Rabe ◽  
Felicia D Rustandy ◽  
Jiyoung Lee ◽  
Marsha Rich Rosner
Keyword(s):  
Extracellular Vesicles ◽  
Triple Negative ◽  
Immune Cell ◽  
List Type ◽  
Breast Cancers ◽  
Tumor Associated Macrophages ◽  
Tumor Associated Macrophage ◽  
Promote Tumor Growth ◽  
Necessary And Sufficient ◽  
First Time

SummaryTriple-negative breast cancers (TNBC) are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumor growth, survival, metastasis and therapeutic resistance. Although cytokines such as CCL5 have been implicated in TAM recruitment to TNBC tumors, the mechanism by which tumor cells educate TAMs is not understood. Here we show that tumor EVs are both necessary and sufficient for programming TAMs toward a pro-metastatic phenotype. The mechanism involves CCL5 regulation of tumor extracellular vesicles (EVs), which activate TLR2 and TLR3, leading to secretion of a common set of cytokines that further stimulate tumor cell invasion and metastasis as well as alter the tumor microenvironment. Cytokine expression is significantly correlated to CCL5 expression and up-regulated in TNBC patient tumors. These results demonstrate for the first time that tumor EVs are key mediators of TAM education, phenocopy the pro-metastatic and drug resistant state of the tumors to TAMs, and illustrate the potential clinical relevance of these findings to TNBC patients.HighlightsTumor extracellular vesicles (EVs) are required for pro-metastatic programming of tumor-associated macrophages (TAMs)Tumor CCL5 and macrophage TLR signaling mediate tumor EV programming of TAMs in TNBCsTumor EVs mediate drug resistance in TAMs and alter recruitment of regulatory T-cells.Cytokines expressed by EV-educated TAMs are enriched and correlate with CCL5 in human TNBC patients.eTOCChemokines such as CCL5 recruit tumor-associated macrophages (TAMs) that are required for metastasis, but TAM programming is not understood. Rabe et al. show that tumor extracellular vesicles (EVs) are required for programming TAMs via Toll-like Receptors (TLRs) to phenocopy the tumor, rewire the microenvironment, drive metastasis and promote immune cell evasion.

scholarly journals Molecular and functional diversity of distinct subpopulations of extracellular vesicles from stressed pancreatic beta cells: implications for autoimmunity

2020 ◽  
Author(s):  
Khem Raj Giri ◽  
Laurence de Beaurepaire ◽  
Dominique Jegou ◽  
Margot Lavy ◽  
Mathilde Mosser ◽  
...  
Keyword(s):  
Beta Cells ◽  
Extracellular Vesicles ◽  
Pancreatic Beta Cells ◽  
Environmental Changes ◽  
Immune Cell ◽  
Active Material ◽  
Fold Increase ◽  
List Type ◽  
Cell Recruitment ◽  
Immune Cell Recruitment

AbstractBeta cell failure and apoptosis following islet inflammation have been associated with autoimmune type 1 diabetes pathogenesis. As conveyors of biological active material, extracellular vesicles (EV) act as mediators in communication with immune effectors fostering the idea that EV from inflamed beta cells may contribute to autoimmunity. Evidence accumulates that beta exosomes promote diabetogenic responses, but relative contributions of larger vesicles as well as variations in the composition of the beta cell’s vesiculome due to environmental changes have not been explored yet. Here, we made side-by-side comparisons of the phenotype and function of apoptotic bodies (AB), microvesicles (MV) and small EV (sEV) isolated from an equal amount of MIN6 beta cells exposed to inflammatory, hypoxic or genotoxic stressors. Under normal conditions, large vesicles represent 93% of the volume, but only 2% of the number of the vesicles. Our data reveal a consistently higher release of AB and sEV and to a lesser extent of MV, exclusively under inflammatory conditions commensurate with a 4-fold increase in the total volume of the vesiculome and enhanced export of immune-stimulatory material including the autoantigen insulin, microRNA, and cytokines. Whilst inflammation does not change the concentration of insulin inside the EV, specific Toll-like receptor-binding microRNA sequences preferentially partition into sEV. Exposure to inflammatory stress engenders drastic increases in the expression of monocyte chemoattractant protein 1 in all EV and of interleukin-27 solely in AB suggesting selective sorting towards EV subspecies. Functional in vitro assays in mouse dendritic cells and macrophages reveal further differences in the aptitude of EV to modulate expression of cytokines and maturation markers. These findings highlight the different quantitative and qualitative imprints of environmental changes in subpopulations of beta EV that may contribute to the spread of inflammation and sustained immune cell recruitment at the inception of the (auto-) immune response.Graphical AbstractInflammation stimulates release of a heterogeneous population of beta EV with differential expression of immunogenic substances involved in immune cell recruitment and activation.HighlightsStress engenders an up to four-fold increase in the volume of the vesiculome and enhanced auto-antigen releaseCytokines are selectively sorted into EV subspeciesTLR-binding microRNAs are enriched in sEVEV from stressed beta cells promote dendritic and macrophage cell activation

scholarly journals Preclinical and Clinical Therapeutic Strategies Affecting Tumor-Associated Macrophages in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
H. Degroote ◽  
A. Van Dierendonck ◽  
A. Geerts ◽  
H. Van Vlierberghe ◽  
L. Devisscher
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Underlying Liver Disease ◽  
Promote Tumor Growth ◽  
Promising Target ◽  
Anticancer Immunity ◽  
Stimulation Of

Hepatocellular carcinoma (HCC) most often develops in patients with underlying liver disease characterized by chronic nonresolving inflammation. Tumor-associated macrophages (TAMs) are one of the most abundant immune cell populations within the tumoral microenvironment. As key actors of cancer-related inflammation, they promote tumor growth by suppression of effective anticancer immunity, stimulation of angiogenesis, and tissue remodeling. Therefore, they have become an attractive and promising target for immunotherapy. The heterogeneity of TAM subtypes and their origin and dynamic phenotype during the initiation and progression of HCC has been partially unraveled and forms the base for the development of therapeutic agents. Current approaches are aimed at decreasing the population of TAMs by depleting macrophages present in the tumor, blocking the recruitment of bone marrow-derived monocytes, and/or functionally reprogramming TAMs to antitumoral behavior. In this review, the preclinical evolution and hitherto clinical trials for TAM-targeted therapy in HCC will be highlighted.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

Interest rate option hedging portfolios without bank account

2019 ◽  
Vol 37 (1) ◽  
pp. 134-142
Author(s):  
Alberto Bueno-Guerrero
Keyword(s):  
Design Methodology ◽  
Contingent Claim ◽  
Necessary And Sufficient Condition ◽  
Barrier Option ◽  
Bank Account ◽  
Content Type ◽  
Option Hedging ◽  
Hedging Portfolio ◽  
Necessary And Sufficient ◽  
First Time

Purpose This paper aims to study the conditions for the hedging portfolio of any contingent claim on bonds to have no bank account part. Design/methodology/approach Hedging and Malliavin calculus techniques recently developed under a stochastic string framework are applied. Findings A necessary and sufficient condition for the hedging portfolio to have no bank account part is found. This condition is applied to a barrier option, and an example of a contingent claim whose hedging portfolio has a bank account part different from zero is provided. Originality/value To the best of the authors’ knowledge, this is the first time that this issue has been addressed in the literature.

scholarly journals Triple-negative breast cancers are increased in black women regardless of age or body mass index

2009 ◽  
Vol 11 (2) ◽  
Author(s):  
Lesley A Stead ◽  
Timothy L Lash ◽  
Jerome E Sobieraj ◽  
Dorcas D Chi ◽  
Jennifer L Westrup ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Black Women ◽  
Body Mass ◽  
Triple Negative ◽  
Breast Cancers

scholarly journals Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Hormone Replacement ◽  
Breast Cancers ◽  
Younger Women ◽  
Alternative Pathways ◽  
Increased Risk ◽  
History Of ◽  
Hormone Sensitive

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

Sign in / Sign up

Export Citation Format

Share Document