Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks

Cell Death and Disease, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 4, 2024

Abstract Current treatment strategies for cancer, especially advanced are limited and unsatisfactory. One of the most substantial advances in cancer therapy, last decades, was discovery a new layer immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate cells by targeting checkpoints. Immune checkpoints type immunosuppressive molecules expressed on cells, regulate degree activation avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy broad applicability across various cancers. Unfortunately, not all patients benefit remarkably from overall response rates to ICIs remain relatively low types. Moreover, primary acquired resistance pose serious challenges clinical application immunotherapy. Thus, deeper understanding molecular biological properties regulatory mechanisms is urgently needed improve options fo r current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, only due their involvement aspects hallmarks, but also impact shaping tumor microenvironment. In this review, we systematically summarize status existing roles circRNAs Meanwhile, aim settle issue an evidence-oriented manner that involved hallmarks effects

Язык: Английский

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Immunoregulatory role of exosomal circRNAs in the tumor microenvironment

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 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.

Язык: Английский

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Recent advances of exosomal circRNAs in cancer and their potential clinical applications

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июль 31, 2023

Abstract Circular RNA (circRNA) is a type of non-coding that forms covalently closed, uninterrupted loop. The expression circRNA differs among cell types and tissues, various circRNAs are aberrantly expressed in variety diseases, including cancer. Aberrantly contribute to disease progression by acting as microRNA sponges, functional protein or novel templates for translation. Recent studies have shown enriched exosomes. Exosomes spherical bilayer vesicles released cells into extracellular spaces mediate intercellular communication delivering cargoes. These cargoes include metabolites, proteins, lipids, molecules. Exosome-mediated cell-cell cell-microenvironment communications influence the carcinogenesis regulating proliferation, angiogenesis, metastasis well immune escape. In this review, we summarize current knowledge about exosomal cancers discuss their specific functions tumorigenesis. Additionally, potential value diagnostic biomarkers applications circRNA-based cancer therapy.

Язык: Английский

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Recent progress in the immunotherapy of hepatocellular carcinoma: Non-coding RNA-based immunotherapy may improve the outcome

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115104 - 115104

Опубликована: Июнь 30, 2023

Hepatocellular carcinoma (HCC) is the second most lethal cancer and a leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) significantly improved prognosis HCC; however, therapeutic response remains unsatisfactory in substantial proportion patients or needs to be further responders. Herein, other methods immunotherapy, including vaccine-based adoptive cell therapy, cytokine delivery, kynurenine pathway inhibition, gene have been adopted clinical trials. Although results were not encouraging enough expedite their marketing. A major human genome transcribed into non-coding RNAs (ncRNAs). Preclinical studies extensively investigated roles ncRNAs different aspects HCC biology. cells reprogram expression pattern numerous decrease immunogenicity HCC, exhaust cytotoxic anti-cancer function CD8 + T cells, natural killer (NK) dendritic (DCs), M1 macrophages, promote immunosuppressive Reg M2 myeloid-derived suppressor (MDSCs). Mechanistically, recruit interact with immune thereby regulating checkpoints, functional receptors enzymes, inflammatory anti-inflammatory cytokines. Interestingly, prediction models based on tissue even serum levels could predict immunotherapy HCC. Moreover, markedly potentiated efficacy ICIs murine This review article first discusses recent advances then dissects involvement potential application

Язык: Английский

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Integrated proteogenomic characterization reveals an imbalanced hepatocellular carcinoma microenvironment after incomplete radiofrequency ablation

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Май 25, 2023

Abstract Background Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed provide further insight into integrated transcriptomic proteogenomic landscape identify a new target involved in HCC progression following iRFA. Methods Peripheral blood matched tissue samples were collected from 10 RFA-treated patients. Multiplex immunostaining flow cytometry used local systemic responses. Differentially expressed genes (DEGs) differentially proteins (DEPs) explored via analyses. Proteinase-3 (PRTN3) was identified these And then, ability of PRTN3 predict overall survival (OS) assessed 70 patients with early recurrence RFA. In vitro CCK-8, wound healing transwell assays conducted observe interactions between Kupffer cells (KCs) induced by PRTN3. The protein levels multiple oncogenic factors signaling pathway components detected western blotting. A xenograft mouse model built tumorigenic effect overexpression on HCC. Results revealed no immediate significant change cell counts periablational tumor tissues 30 min Flow showed significantly increased CD4 + T cells, CD8 CD25 CD127 − Tregs decreased CD16 CD56 natural killer day 5 cRFA ( p < 0.05). Transcriptomics proteomics 389 DEGs 20 DEPs. Pathway analysis that DEP-DEGs mainly enriched immunoinflammatory response, cancer metabolic processes. Among DEP-DEGs, persistently upregulated closely associated OS recurrent KCs may affect migration invasion heat stress-treated cells. promotes growth PI3K/AKT P38/ERK pathways. Conclusions provides comprehensive overview response landscapes milieu iRFA, revealing Trial registration ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588 .

Язык: Английский

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The current status and future of PD-L1 in liver cancer

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 12, 2023

The application of immunotherapy in tumor, especially immune checkpoint inhibitors (ICIs), has played an important role the treatment advanced unresectable liver cancer. However, efficacy ICIs varies greatly among different patients, which aroused people’s attention to regulatory mechanism programmed death ligand-1 (PD-L1) escape PD-L1 is regulated by multiple levels and signaling pathways hepatocellular carcinoma (HCC), including gene variation, epigenetic inheritance, transcriptional regulation, post-transcriptional post-translational modification. More studies have also found that high expression may be main factor affecting what difference expressed types cells microenvironment HCC, type determines effect tumor remains unclear. Therefore, clarifying cancer can provide more basis for combined strategy. In addition its well-known plays a regulating cell proliferation promoting drug resistance cells, will reviewed this paper. addition, we summarized natural products drugs HCC.

Язык: Английский

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Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities

MedComm, Год журнала: 2024, Номер 5(12)

Опубликована: Ноя. 24, 2024

Exosomes can regulate the malignant progression of tumors by carrying a variety genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, immune escape. In microenvironment (TME), circRNAs be transferred among cells, endothelial cancer-associated fibroblasts, microbiota, affecting initiation progression. Due high stability widespread presence circRNAs, they hold promise biomarkers for diagnosis prognosis prediction blood urine. addition, designing nanoparticles targeting utilizing derived from cells or stem provide new strategies cancer therapy. this review, we examined crucial role regulating tumor-related signaling pathways summarized transmission between various types their impact on TME. Finally, our review highlights potential diagnostic prognostic biomarkers, well suggesting clinical

Язык: Английский

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Role of exosomes in hepatocellular carcinoma and the regulation of traditional Chinese medicine

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Янв. 17, 2023

Hepatocellular carcinoma (HCC) usually occurs on the basis of chronic liver inflammatory diseases and cirrhosis. The microenvironment plays a vital role in tumor initiation progression. Exosomes, which are nanometer-sized membrane vesicles secreted by number cell types. Exosomes carry multiple proteins, DNAs various forms RNA, mediators cell-cell communication regulate microenvironment. In recent decade, many studies have demonstrated that exosomes involved between HCC cells stromal cells, including endothelial macrophages, hepatic stellate immune serve as regulator proliferation metastasis, evasion immunotherapy. addition, can also be used for diagnosis treatment HCC. They potentially specific biomarkers early drug delivery vehicles Chinese herbal medicine, is widely prevention China, may release exosomes-mediated intercellular communication. this review, we summarized latest progresses initiation, progression potential value Traditional medicine biological behaviors

Язык: Английский

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Crosstalk Between circRNA and Tumor Microenvironment of Hepatocellular Carcinoma: Mechanism, Function and Applications

OncoTargets and Therapy, Год журнала: 2024, Номер Volume 17, С. 7 - 26

Опубликована: Янв. 1, 2024

Abstract: Hepatocellular carcinoma (HCC) is one of the most common aggressive tumors in world. Despite availability various treatments, its prognosis remains poor due to lack specific diagnostic indicators and high heterogeneity HCC cases. CircRNAs are noncoding RNAs with stable highly expression. Extensive research evidence suggests that circRNAs mediate pathogenesis progression through acting as miRNA sponges, protein modulators, translation templates. Tumor microenvironment (TME) has become a hotspot immune-related recent years effects on metabolism, secretion immunity HCC. Accordingly, understanding role played by TME important for study This review will discuss crosstalk between In addition, we current deficiencies controversies predict future directions. Keywords: CircRNAs, hepatocellular carcinoma, characteristics, tumor microenvironment, biomarker

Язык: Английский

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Advances in the roles and molecular mechanisms of exosomal circular RNAs in regulating the pre-metastatic niche of tumors

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 19, 2025

Metastasis remains a major cause of morbidity and mortality in patients with malignant tumors. The pre-metastatic niche is prerequisite for distant metastasis driven by primary Circular RNAs (circRNAs), class single-stranded closed non-coding RNAs, exhibit high stability, evolutionary conservation, cell-type specificity. Exosomes, as natural carriers circRNAs, mediate intercellular communication contribute to the formation niche; however, mechanisms which they do so remain incompletely understood. This review summarizes biological characteristics functions exosomal circRNAs outlines molecular pathways through shape tumor microenvironment, emphasis on immunosuppression, vascular permeability, extracellular matrix remodeling, lymphangiogenesis. first focus functional roles regulation, providing basis development therapeutic strategies targeting metastatic progression.

Язык: Английский

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