Melanoma Derived Exosomes Amplify Radiotherapy Induced Abscopal Effect via IRF7/I‐IFN Axis in Macrophages DOI Creative Commons
Lu Wang,

Kangjie Shen,

Zixu Gao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 29, 2024

Abstract Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as abscopal effect. However, detailed underlying mechanisms remain largely unknown. A tumor‐bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single‐cell RNA sequencing, immunofluorescence, flow cytometry are performed to explore regulation of microenvironment (TME) RT. series in vitro assays, including luciferase reporter, Pulldown, fluorescent situ hybridization (FISH) evaluate mechanism In addition, vivo assays investigate combination therapy strategies for enhancing The results showed that RT significantly inhibited localized metastasis progression improved TME. Mechanistically, promoted release tumor‐derived exosomes carrying circPIK3R3, which taken up macrophages. circPIK3R3 Type I interferon (I‐IFN) secretion M1 polarization via miR‐872‐3p/IRF7 axis. Secreted I‐IFN activated JAK/STAT signaling pathway CD8 + T cells, IFN‐γ GZMB secretion. Together, study shows promote circPIK3R3/miR‐872‐3p/IRF7 axis macrophages enhance anti‐tumor immune response cells.

Language: Английский

The biology, function, and applications of exosomes in cancer DOI Creative Commons
Jinyi Liu,

Liwen Ren,

Sha Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 11(9), P. 2783 - 2797

Published: Jan. 10, 2021

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication activate signaling pathways in target cells. In cancers, exosomes may participate growth metastasis tumors by regulating immune response, blocking epithelial-mesenchymal transition, promoting angiogenesis. also involved development resistance chemotherapeutic drugs. liquid biopsies be used as non-invasive biomarkers early detection diagnosis cancers. Because their amphipathic structure, natural drug delivery vehicles cancer therapy.

Language: Английский

Citations

379

Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer DOI Creative Commons
Hongbo Wang, Zaiming Lu, Xiangxuan Zhao

et al.

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Dec. 1, 2019

Abstract Hepatocellular carcinoma (HCC, also called primary liver cancer) is one of the most fatal cancers in world. Due to insidiousness onset HCC and lack effective treatment methods, prognosis extremely poor, 5-year average survival rate less than 10%. Exosomes are nano-sized microvesicle contain various components such as nucleic acids, proteins, lipids. important carriers for signal transmission or transportation material from cell between cells tissues. In recent years, exosomes have been considered potential therapeutic targets HCC. A large number reports indicate that play a key role establishment an microenvironment, well development, progression, invasion, metastasis, even diagnosis, treatment, However, exact molecular mechanisms roles these processes remain unclear. We believe elucidation regulatory mechanism HCC-related its signaling pathway analysis clinical applications diagnosis can provide useful clues future regimens This article discusses summarizes research progress their applications.

Language: Английский

Citations

234

Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression DOI Creative Commons

Yunzhou Pu,

Qing Ji

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 3, 2022

Anti-programmed cell death 1 (PD-1) or anti-PD-ligand (L) drugs, as classic immune checkpoint inhibitors, are considered promising treatment strategies for tumors. In clinical practice, some cancer patients experience drug resistance and disease progression in the process of anti-PD-1/PD-L1 immunotherapy. Tumor-associated macrophages (TAMs) play key roles regulating PD-1/PD-L1 immunosuppression by inhibiting recruitment function T cells through cytokines, superficial ligands, exosomes. There several therapies available to recover anticancer efficacy inhibitors targeting TAMs, including inhibition TAM differentiation re-education activation. this review, we will summarize mechanisms TAMs blocker resistance. Furthermore, discuss that were designed deplete re-educate intervene with chemokines secreted exosomes from M1 macrophages, providing more potential options improve inhibitors.

Language: Английский

Citations

180

Rapid and sensitive exosome detection with CRISPR/Cas12a DOI
Xianxian Zhao, Wenqing Zhang,

Xiaopei Qiu

et al.

Analytical and Bioanalytical Chemistry, Journal Year: 2020, Volume and Issue: 412(3), P. 601 - 609

Published: Jan. 1, 2020

Language: Английский

Citations

159

Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles DOI Creative Commons
Elisabetta Chiaradia, Brunella Tancini, Carla Emiliani

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1763 - 1763

Published: July 12, 2021

Under physio-pathological conditions, cells release membrane-surrounded structures named Extracellular Vesicles (EVs), which convey their molecular cargo to neighboring or distant influencing metabolism. Besides involvement in the intercellular communication, EVs might represent a tool used by eliminate unnecessary/toxic material. Here, we revised literature exploring link between and redox biology. The first proof of this derives from evidence demonstrating that healthy protect target oxidative insults through transfer antioxidants. Oxidative stress conditions influence that, turn, modulate status cells. stress-related exert both beneficial harmful effects, as they can carry antioxidants ROS-generating enzymes oxidized molecules. As mediators cell-to-cell are also implicated pathophysiology diseases. review found numerous studies speculated on role signaling pathologies, but few them unraveled mechanisms behind complex link. Thus, purpose is report discuss evidence, highlighting analysis content stress-released (reminiscent originating cells), starting point for use diagnostic therapeutic tools

Language: Английский

Citations

131

The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism DOI Open Access

Lingyu Tian,

Daniel J. Smit, Manfred Jücker

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2652 - 2652

Published: Jan. 31, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition

Language: Английский

Citations

129

Preserving extracellular vesicles for biomedical applications: consideration of storage stability before and after isolation DOI Creative Commons

Fumin Yuan,

Yamin Li,

Zhuhui Wang

et al.

Drug Delivery, Journal Year: 2021, Volume and Issue: 28(1), P. 1501 - 1509

Published: Jan. 1, 2021

Extracellular vesicles (EVs) are nanovesicles released by various cell types. EVs known for cell-to-cell communications and have potent biological activities. Despite great progress in recent years studies exploring the potentials of early disease detection, therapeutic application drug delivery, determination favorable storage conditions has been challenging. The understanding impact on before after isolation is still limited. Storage may change size, number, contents, functions, behaviors EVs. Here, we summarized current about stability different conditions, focusing temperatures, durations, freezing thawing cycles. –80 °C seems to remain most condition biofluids isolated EVs, while be stored at 4 shortly. Lyophilization promising EV products. Challenges storage-mediated development advanced preservation techniques

Language: Английский

Citations

118

Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway DOI Creative Commons
Shuhai Chen, Yuji Morine, Kazunori Tokuda

et al.

International Journal of Oncology, Journal Year: 2021, Volume and Issue: 59(2)

Published: July 1, 2021

Targeting the tumor stroma is an important strategy in cancer treatment. Cancer‑associated fibroblasts (CAFs) and tumor‑associated macrophages (TAMs) are two main components microenvironment (TME) hepatocellular carcinoma (HCC), which can promote progression. Plasminogen activator inhibitor‑1 (PAI‑1) upregulation HCC predictive of unfavorable behavior prognosis. However, crosstalk between cells, TAMs CAFs, functions PAI‑1 remain to be fully investigated. In present study, macrophage polarization key paracrine factors were assessed during their interactions with CAFs cells. Cell proliferation, wound healing Transwell Matrigel assays used investigate malignant cells vitro. It was found that induced M2 by upregulating mRNA expression levels CD163 CD206, downregulating IL‑6 secretion macrophages. Both derived from promoted cell proliferation invasion. Furthermore, upregulated after being stimulated CAF‑conditioned medium mediating epithelial‑mesenchymal transition. producer C‑X‑C motif chemokine ligand 12 (CXCL12) TME CXCL12 contributed induction TAMs. conclusion, results study suggested via CXCL12. it produced enhanced Therefore, these may targets for inhibiting

Language: Английский

Citations

112

Tumor associated macrophages-derived exosomes facilitate hepatocellular carcinoma malignance by transferring lncMMPA to tumor cells and activating glycolysis pathway DOI Creative Commons
Minghao Xu, Chenhao Zhou, Jialei Weng

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Aug. 19, 2022

Tumor-associated macrophages (TAMs), which form a large part of the tumor microenvironment, are normally regulated by metabolic reprogramming. However, potential mechanisms immune-metabolism interaction between hepatocellular carcinoma (HCC) cells and TAMs remain unclear.The candidate long non-coding RNAs (lncRNAs) were screened Smart-seq based scRNA-seq method then validated qPCR. Immunostaining analysis was done to examine levels markers for glycolysis. Exosomes from primary human HCC tissues isolated centrifugation, their internalization with lncRNAs confirmed immunofluorescence. The underlying mechanism TAMs-derived exosomal lncRNA luciferase reporter assay RNA immunoprecipitation. Metabolism regulation evaluated through glucose consumption, lactate productions extracellular acidification rates (ECARs). Mouse xenograft models used elucidate in vivo effect on growth.TAMs augment aerobic glycolysis proliferation exosome transmission myeloid-derived lncRNA, M2 macrophage polarization associated (lncMMPA). Mechanistically, lncMMPA not only could polarize macrophage, but also act as an microRNA sponge interact miR-548 s increase mRNA level ALDH1A3, further promote metabolism cell HCC. Moreover, increased multiplication interacting vivo. Clinically, expression associates reduced survival patients.LncMMPA plays important role regulating malignancy reprogramming s/ALDH1A3 pathway.

Language: Английский

Citations

91

Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options DOI

Reza Moshrefiravasjani,

Amin Kamrani,

Nazanin Nazari

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 254, P. 155083 - 155083

Published: Jan. 3, 2024

Language: Английский

Citations

19