Targeting the epigenome to reinvigorate T cells for cancer immunotherapy DOI Creative Commons

Dian Xiong,

Lu Zhang, Zhi‐Jun Sun

et al.

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Dec. 4, 2023

Abstract Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field of cancer treatment; however, ICI efficacy is constrained by progressive dysfunction CD8 + tumor-infiltrating lymphocytes (TILs), which termed T cell exhaustion. This process driven diverse extrinsic factors across heterogeneous tumor immune microenvironment (TIME). Simultaneously, tumorigenesis entails robust reshaping epigenetic landscape, potentially instigating In this review, we summarize mechanisms governing microenvironmental cues leading to exhaustion, and discuss therapeutic potential targeting regulators for immunotherapies. Finally, outline conceptual technical advances in developing treatment paradigms involving immunostimulatory agents therapies.

Language: Английский

Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma DOI Creative Commons
Zongqiang Hu, Gang Chen,

Yingpeng Zhao

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 18, 2023

Abstract Background Circular RNAs (circRNAs) can be encapsulated into exosomes to participate in intercellular communication, affecting the malignant progression of a variety tumors. Dysfunction CD8 + T cells is main factor immune escape from hepatocellular carcinoma (HCC). Nevertheless, effect exosome-derived circRNAs on T-cell dysfunction needs further exploration. Methods The circCCAR1 tumorigenesis and metastasis HCC was assessed by vitro vivo functional experiments. function measured enzyme-linked immunosorbent assay (ELISA), western blotting flow cytometry. Chromatin immunoprecipitation, biotinylated RNA pull-down, MS2 pull-down assays were used exploration mechanism. A mouse model with reconstituted human system components (huNSG mice) constructed explore role exosomal resistance anti-PD1 therapy HCC. Results Increased levels existed tumor tissues plasma patients, culture supernatant cells. CircCCAR1 accelerated growth vivo. E1A binding protein p300 (EP300) eukaryotic translation initiation 4A3 (EIF4A3) promoted biogenesis circCCAR1, Wilms 1-associated (WTAP)-mediated m6A modification enhanced stability insulin-like 2 mRNA-binding 3 (IGF2BP3). acted as sponge for miR-127-5p upregulate its target WTAP feedback loop comprising circCCAR1/miR-127-5p/WTAP axis formed. secreted heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1)-dependent manner. Exosomal taken caused stabilizing PD-1 protein. immunotherapy. Furthermore, increased cell division cycle apoptosis regulator 1 (CCAR1) induced EP300 CCAR1 β-catenin protein, which transcription PD-L1. Conclusions enhances released contributes immunosuppression facilitating induces immunotherapy, providing potential therapeutic strategy patients.

Language: Английский

Citations

180
Engineered extracellular vesicles and their mimetics for cancer immunotherapy DOI

Chunping Liu,

Yichao Wang, Longmei Li

et al.

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 349, P. 679 - 698

Published: July 28, 2022

Language: Английский

Citations

109
Exosomal circRNA: emerging insights into cancer progression and clinical application potential DOI Creative Commons
Fan Zhang, Jiajia Jiang, Hui Qian

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 26, 2023

Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.

Language: Английский

Citations

99
Comprehensive analysis of scRNA-Seq and bulk RNA-Seq reveals dynamic changes in the tumor immune microenvironment of bladder cancer and establishes a prognostic model DOI Creative Commons
Zhiyong Tan, Xiaorong Chen,

Jieming Zuo

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 27, 2023

Abstract Background The prognostic management of bladder cancer (BLCA) remains a great challenge for clinicians. Recently, bulk RNA-seq sequencing data have been used as marker many cancers but do not accurately detect core cellular and molecular functions in tumor cells. In the current study, single-cell RNA (scRNA-seq) were combined to construct model BLCA. Methods BLCA scRNA-seq downloaded from Gene Expression Omnibus (GEO) database. Bulk obtained UCSC Xena. R package "Seurat" was processing, uniform manifold approximation projection (UMAP) utilized downscaling cluster identification. FindAllMarkers function identify genes each cluster. limma obtain differentially expressed (DEGs) affecting overall survival (OS) patients. Weighted gene correlation network analysis (WGCNA) key modules. intersection cells modules DEGs by univariate Cox Least Absolute Shrinkage Selection Operator (LASSO) analyses. Differences clinicopathological characteristics, immune microenvironment, checkpoints, chemotherapeutic drug sensitivity between high low-risk groups also investigated. Results analyzed 19 cell subpopulations 7 types. ssGSEA showed that all types significantly downregulated samples We identified 474 dataset, 1556 2334 associated with module WGCNA. After performing intersection, Cox, LASSO analysis, we based on expression levels 3 signature genes, namely MAP1B, PCOLCE2, ELN. feasibility validated an internal training set two external validation sets. Moreover, patients high-risk scores are predisposed experience poor OS, larger prevalence stage III-IV, greater TMB, higher infiltration cells, lesser likelihood responding favorably immunotherapy. Conclusion By integrating data, constructed novel predict risk score is promising independent factor closely correlated microenvironment characteristics.

Language: Английский

Citations

88
The function and mechanisms of action of circular RNAs in Urologic Cancer DOI Creative Commons
Zi-Hao Zhang, Yue Wang, Ya Zhang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 25, 2023

Abstract Kidney, bladder, and prostate cancer are the three major tumor types of urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding with a stabile structure unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs widely distributed within body, important biologic functions such as sponges for microRNAs, RNA binding proteins, templates regulation transcription protein translation. The abnormal expression circRNAs in vivo is significantly associated development tumors. now emerged potential biomarkers diagnosis prognosis tumors, well targets new therapies. Although we gained better understanding circRNA, there still many questions to be answered. In this review, summarize properties detail their function, focusing on effects circRNA proliferation, metastasis, apoptosis, metabolism, drug resistance kidney, cancers.

Language: Английский

Citations

54
Exosomal circRNAs: Novel biomarkers and therapeutic targets for urinary tumors DOI
Qiang Liu, Shenglong Li

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216759 - 216759

Published: Feb. 28, 2024

Language: Английский

Citations

24
New insights on anti-tumor immunity of CD8+ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy DOI Creative Commons

Yibin Lin,

Yifu Song, Yaochuan Zhang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 17, 2025

Abstract Recent breakthroughs in tumor immunotherapy have confirmed the capacity of immune system to fight several cancers. The effective means treating cancer involves accelerating death cells and improving patient immunity. Dynamic changes microenvironment alter actual effects anti-tumor drug production may trigger favorable or unfavorable responses by modulating tumor-infiltrating lymphocytes. Notably, CD8 + T are one primary that provide response. Tumor stem will resist evade destruction through various mechanisms as exert their function. This paper reviews research on regulation development prognosis directly indirectly role cells. We also discuss related strategies.

Language: Английский

Citations

3
Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity DOI Creative Commons

Can Can,

Xinyu Yang,

Hexiao Jia

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 6, 2025

Drug resistance and immune escape continue to contribute poor prognosis in AML. Increasing evidence suggests that exosomes play a crucial role AML microenvironment. Sanger sequencing, RNase R fluorescence situ hybridization were performed confirm the existence of circ_0006896. The circ_0006896 progression was assessed by vitro vivo functional experiments. Flow cytometry, RT-qPCR adoptive T cell-transfer immunotherapy conducted assess function exosomal CD8+ cell dysfunction. RNA pull-down assay, mass spectrometry, immunofluorescence, co-immunoprecipitation western blot identify interacting proteins. CircRNA expression patterns differ significantly between controls compared lncRNAs or mRNAs. A new circRNA, circ_0006896, is upregulated both cells correlates with relapse In studies suggest promotes proliferation, reduces chemotherapy sensitivity, more importantly, impairs efficacy immunotherapy. Mechanistically, physically interacts catalytic domain histone deacetylase HDAC1, decreasing H3 acetylation, impairing transcription genes involved arachidonic acid metabolism, ultimately inhibiting lipid peroxidation ferroptosis cells. Exosomal disrupts LEF1 subsequently cytotoxic molecules IFN-γ Granzyme B. We demonstrate self-driven mediated circRNAs cells, highlighting potential targeting

Language: Английский

Citations

2
Immunoregulatory role of exosomal circRNAs in the tumor microenvironment DOI Creative Commons
Changsheng Lv,

Jinhao Chen,

Yuxiang Wang

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 17, 2025

As cancer incidence and mortality rates rise, there is an urgent need to develop effective immunotherapy strategies. Circular RNA (circRNA), a newly identified type of non-coding RNA, abundant within cells can be released via exosomes, facilitating communication between cells. Studies have demonstrated that exosomal circRNAs alter the tumor microenvironment modulate immune responses by influencing functions T cells, natural killer (NK) macrophages, thereby enabling tumors evade system. Moreover, show potential as diagnostic biomarkers therapeutic targets for cancer. This review summarizes regulatory roles in their applications progression treatment, highlighting promise improving immunotherapy. Future research should concentrate on understanding mechanisms key developing targeted methods.

Language: Английский

Citations

2
The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis DOI Creative Commons

Wujun Chen,

Jiazhen Xu,

Yudong Wu

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(9), P. 2879 - 2896

Published: Jan. 1, 2023

Cholesterol levels are an initiating risk factor for atherosclerosis. Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2. Especially, and EBP promising therapeutic targets drug development due to many drugs have been approved entered into clinical research by targeting these genes. However, new still need be discovered. Interestingly, small nucleic acid vaccines were the market, Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran. agents all linear RNA agents. Circular RNAs (circRNAs) may longer half-lives, higher stability, lower immunogenicity, production costs, delivery efficiency than their covalently closed structures. CircRNA developed several companies, Orna Therapeutics, Laronde, CirCode, Therorna. studies shown that circRNAs regulate synthesis regulating ACS, YWHAG, PTEN, SREBP-2, PMK expression. MiRNAs essential circRNA-mediated biosynthesis. Notable, phase II trial inhibiting miR-122 with has completed. Suppressing circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, circFOXO3 target development, specifically circFOXO3. This review focuses on mechanism of circRNA/miRNA axis hope providing knowledge identify targets.

Language: Английский

Citations

40