The glycosylation in SARS-CoV-2 and its receptor ACE2

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 15, 2021

Coronavirus disease 2019 (COVID-19), a highly infectious caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 235 million individuals and led to 4.8 deaths worldwide as of October 5 2021. Cryo-electron microscopy topology show that the SARS-CoV-2 genome encodes lots glycosylated proteins, such spike (S), envelope (E), membrane (M), ORF3a which are responsible for host recognition, penetration, binding, recycling pathogenesis. Here we reviewed detections, substrates, biological functions glycosylation in proteins well human receptor ACE2, also summarized approved undergoing therapeutics associated with glycosylation. This review may not only broad understanding viral glycobiology, but provide key clues development new preventive therapeutic methodologies against its variants.

Language: Английский

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D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(8)

Published: Feb. 18, 2022

Significance PD-L1 is well known as an immune checkpoint molecule, which suppresses surveillance through binding to its receptor PD-1. Intracellular can also protect messenger RNAs of several DNA damage repair–related genes from degradation and enhance tumor resistance DNA-damaging therapy. Triple-negative breast cancer (TNBC) has the worst prognosis highest risk distant relapse in shows immunotherapy radiotherapy. In this study, we found that D-mannose promote significantly radiotherapy TNBC. Since TNBC treatment still a clinical challenge, our findings provide strategies therapeutic efficacy may have application.

Language: Английский

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Advances in immunotherapy for triple-negative breast cancer

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

Published: Sept. 2, 2023

Immunotherapy has recently emerged as a treatment strategy which stimulates the human immune system to kill tumor cells. Tumor immunotherapy is based on editing, enhances antigenicity of cells and increases tumoricidal effect It also suppresses immunosuppressive molecules, activates or restores function, anti-tumor responses, inhibits growth f cell. This offers possibility reducing mortality in triple-negative breast cancer (TNBC).Immunotherapy approaches for TNBC have been diversified recent years, with breakthroughs this entity. Research checkpoint inhibitors (ICIs) made it possible identify different molecular subtypes formulate individualized schedules. review highlights unique microenvironment integrates analyzes advances ICI therapy. discusses strategies combination ICIs chemotherapy, radiation therapy, targeted emerging methods such nanotechnology, ribonucleic acid vaccines, gene Currently, numerous ongoing completed clinical trials are exploring utilization conjunction existing modalities TNBC. The objective these investigations assess effectiveness various combined determine most effective regimens patients TNBC.This provides insights into used overcome drug resistance immunotherapy, explores directions development

Language: Английский

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Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Oct. 25, 2022

Immunotherapy for cancer is a rapidly developing treatment that modifies the immune system and enhances antitumor response. B7-H3 (CD276), member of B7 family plays an immunoregulatory role in T cell response, has been highlighted as novel potential target immunotherapy. shown to play inhibitory activation proliferation, participate tumor evasion influence both response behavior through different signaling pathways. expression found be aberrantly upregulated many types, association between poor prognosis established. targeting approaches rapidly, ongoing clinical trials are exploring safety efficacy profiles these therapies cancer. In this review, we summarize emerging research on function underlying pathways B7-H3, roles advances B7-H3-targeted therapy. Considering microenvironment characteristics results from preclinical models practice, indicates promising future immunotherapy, which might eventually contribute improvement immunotherapy will benefit patients.

Language: Английский

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New frontiers in immune checkpoint B7-H3 (CD276) research and drug development

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

Published: March 2, 2023

B7-H3 (CD276), a member of the B7 family proteins, is key player in cancer progression. This immune checkpoint molecule selectively expressed both tumor cells and within microenvironment. In addition to its function, has been linked cell proliferation, metastasis, therapeutic resistance. Furthermore, drastic difference protein expression levels between normal tissues suggests that targeting with drugs would lead cancer-specific toxicity, minimizing harm healthy cells. These properties make promising target for therapy.Recently, important advances research drug development have reported, these new findings, including involvement cellular metabolic reprograming, stem enrichment, senescence obesity, expanded our knowledge understanding this molecule, which guiding future strategies B7-H3. review, we briefly discuss biology function development. We emphasize more on latest findings their underlying mechanisms reflect research. addition, improvements B-H3 inhibitors

Language: Английский

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Disrupting the phase separation of KAT8–IRF1 diminishes PD-L1 expression and promotes antitumor immunity

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(3), P. 382 - 400

Published: March 9, 2023

Abstract Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because elusive mechanisms regulating PD-1/PD-L1. Here, we report that cells exposed to interferon-γ (IFNγ), KAT8 undergoes phase separation with induced IRF1 and forms biomolecular condensates upregulate PD-L1. Multivalency from both specific promiscuous interactions between is required for condensate formation. KAT8–IRF1 condensation promotes K78 acetylation binding CD247 (PD-L1) promoter further enriches transcription apparatus promote PD-L1 mRNA. Based on mechanism formation, identified 2142–R8 blocking peptide, which disrupts formation consequently inhibits expression enhances antitumor immunity vitro vivo. Our findings reveal key role regulation provide competitive peptide enhance immune responses.

Language: Английский

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Glycosylation: mechanisms, biological functions and clinical implications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 5, 2024

Protein post-translational modification (PTM) is a covalent process that occurs in proteins during or after translation through the addition removal of one more functional groups, and has profound effect on protein function. Glycosylation most common PTMs, which polysaccharides are transferred to specific amino acid residues by glycosyltransferases. A growing body evidence suggests glycosylation essential for unfolding various activities organisms, such as playing key role regulation function, cell adhesion immune escape. Aberrant also closely associated with development diseases. Abnormal patterns linked emergence health conditions, including cancer, inflammation, autoimmune disorders, several other However, underlying composition structure glycosylated have not been determined. It imperative fully understand internal differential expression glycosylation, incorporate advanced detection technologies keep knowledge advancing. Investigations clinical applications focused sensitive promising biomarkers, effective small molecule targeted drugs emerging vaccines. These studies provide new area novel therapeutic strategies based glycosylation.

Language: Английский

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The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

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

Published: Feb. 8, 2022

Hypoxia is an environmental stressor that instigated by low oxygen availability. It fuels the progression of solid tumors driving tumor plasticity, heterogeneity, stemness and genomic instability. metabolically reprograms microenvironment (TME), adding insult to injury acidic, nutrient deprived poorly vascularized conditions act dampen immune cell function. Through its impact on key cancer hallmarks creating a physical barrier conducive survival, hypoxia modulates escape from mounted response. The cell-immune crosstalk in context hypoxic TME tips balance towards cold immunosuppressed resistant checkpoint inhibitors (ICI). Nonetheless, evidence emerging could make asset for improving response ICI. Tackling contexture has taken silico , digitalized approach with increasing number studies applying bioinformatics deconvolute cellular non-cellular elements TME. Such approaches have additionally been combined signature-based proxies further dissect turbulent hypoxia-immune relationship. In this review we will be highlighting mechanisms which impacts functions how translate predicting immunotherapy era machine learning computational biology.

Language: Английский

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Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics

Theranostics, Journal Year: 2023, Volume and Issue: 13(8), P. 2605 - 2615

Published: Jan. 1, 2023

Cell surface glycosylation has a variety of functions, and its dysregulation in cancer contributes to impaired signaling, metastasis the evasion immune responses.Recently, number glycosyltransferases that lead altered have been linked reduced anti-tumor responses: B3GNT3, which is implicated PD-L1 triple negative breast cancer, FUT8, through fucosylation B7H3, B3GNT2, confers resistance T cell cytotoxicity.Given increased appreciation relevance protein glycosylation, there critical need for development methods allow an unbiased interrogation status.Here we provide overview broad changes at describe selected examples receptors with aberrant leading functional changes, emphasis on checkpoint inhibitors, growth-promoting growth-arresting receptors.Finally, posit field glycoproteomics matured extent where large-scale profiling intact glycopeptides from feasible poised discovery new actionable targets against cancer.

Language: Английский

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Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(7), P. 694 - 713

Published: April 17, 2023

Language: Английский

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