Heterocyclic-Modified Imidazoquinoline Derivatives: Selective TLR7 Agonist Regulates Tumor Microenvironment against Melanoma DOI
Jiaxin Ou, Lu Zheng, Yanlin Chen

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(5), P. 3321 - 3338

Published: Feb. 16, 2024

Immunotherapy targeting the toll-like receptor 7 (TLR7) is a promising strategy for cancer treatment. Herein, we describe design and synthesis of series imidazoquinoline-based TLR7 agonists assess NF-κB pathway activation using HEK-Blue hTLR7 cells to identify most potent small-molecule agonist, SMU-L11 (EC50 = 0.024 ± 0.002 μM). In vitro experiments demonstrated that specifically activated TLR7, resulting in recruitment MyD88 adaptor protein MAPK signaling pathways. Moreover, was found exert immune-enhancing effects by significantly inducing secretion proinflammatory cytokines murine dendritic cells, macrophages, human peripheral blood mononuclear while promoting M1 macrophage polarization. vivo studies B16-F10 mouse tumor model showed enhanced immune cell augmented CD4+ T CD8+ T-cell proliferation, directly killing inhibiting growth.

Language: Английский

Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy DOI Creative Commons
Seyed Hossein Kiaie,

Hossein Salehi‐Shadkami,

Mohammad‐Javad Sanaei

et al.

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

Published: Sept. 21, 2023

Abstract Immune checkpoint (ICP) molecules expressed on tumor cells can suppress immune responses against tumors. ICP therapy promotes anti-tumor by targeting inhibitory and stimulatory pathways of like T dendritic (DC). The investigation into the combination therapies through novel inhibitors (ICIs) has been limited due to immune-related adverse events (irAEs), low response rate, lack optimal strategy for combinatorial cancer immunotherapy (IMT). Nanoparticles (NPs) have emerged as powerful tools promote multidisciplinary cooperation. feasibility efficacy targeted delivery ICIs using NPs overcome primary barrier, improve therapeutic efficacy, provide a rationale more clinical investigations. Likewise, conjugate or encapsulate ICIs, including antibodies, RNAs, small molecule inhibitors. Therefore, combining drug system (DDS) with could profitable immunotherapeutic treatment. This article reviews significant controlled DDS current data from pre-clinical trials mono- IMT limitations. Graphical

Language: Английский

Citations

37
Uncovering the specificity and predictability of tryptophan metabolism in lactic acid bacteria with genomics and metabolomics DOI Creative Commons

Tong Pan,

Zhangming Pei, Zhifeng Fang

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: March 13, 2023

Tryptophan is metabolized by microorganisms into various indole derivatives that have been proven to alleviate diseases and promote human health. Lactic acid bacteria (LAB) are a broad microbial concept, some of which developed as probiotics. However, the capacity most LAB metabolize tryptophan unknown. In this study, aim reveal rule metabolism in multi-omics. The findings showed were rich genes for catabolism multiple shared among species. Although number their homologous sequences was different, they could still form same metabolic enzyme system. metabolomic analysis revealed capable producing variety metabolites. Strains belonging species can produce metabolites similar yields. A few strains strain-specificity production indole-3-lactic (ILA), indole-3-acetic acid, 3-indolealdehyde (IAld). genotype-phenotype association analysis, found be highly consistent with outcomes gene prediction, particularly ILA, indole-3-propionic indole-3-pyruvic acid. overall prediction accuracy more than 87% on average, indicated predictability LAB. Additionally, influenced concentration levels ILA IAld significantly correlated numbers aromatic amino aminotransferase amidase, respectively. unique indolelactate dehydrogenase Ligilactobacillus salivarius primary factor contributing its large ILA. summary, we demonstrated distribution level explored correlation between phenotypes. specificity proven. These results provide novel genomic method discovery potential offer experimental data probiotics specific

Language: Английский

Citations

32
A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response DOI Creative Commons
Song‐Bin Guo, Sheng Du,

Ke-Yu Cai

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(6), P. e17075 - e17075

Published: June 1, 2023

Nrf2, an essential and fascinating transcription factor, enjoys a dual property in the occurrence development of inflammation cancer. For over two decades, numerous studies regarding Nrf2 cancer have been reported, whereas there is still lack scientometrics visualization analysis Hence, scientometric study oxidative stress modulator was implemented.After quality screening, we defined 7168 relevant from 2000 to 2021. CiteSpace, VOSviewer, R software, GraphPad Prism were used for following analysis, including field profiles, research hotspots, future predictions.The total number publications citations are 1058 54,690, respectively. After polynomial fitting curve prediction functions annual publication (y = 3.3909x2 - 13585x + 1 E+07) citation (185.45x2 743669x 7 E+08) generated. found that Biochemistry Molecular Biology correlates with highly, Free Radical Medicine good choice submitting Nrf2-related manuscripts. The current hotspots mainly focus on therapy its cellular molecular mechanisms. "antioxidant response element (87.5)", "gene expression (43.98)", responsive (21.14)", "chemoprevention (20.05)", "carcinogenesis (19.2)", "cancer chemoprevention (18.45)", "free radical (17.15)", "response (14.17)", "chemopreventive agent (14.04)" important study. In addition, "glutathione-S-transferase (47)", "keap1 (15.39)", "heme oxygenase gene (24.35)" cell fate More interestingly, by performing "InfoMap" algorithm, thematic map showed "immune response" but not well developed, indicating it deserves further exploration.This revealed directions research, our findings will offer vigorous roadmap this field.

Language: Английский

Citations

28
Small-molecule agents for cancer immunotherapy DOI Creative Commons
Fang Wang, Kai Fu, Yujue Wang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 905 - 952

Published: Dec. 16, 2023

Cancer immunotherapy, exemplified by the remarkable clinical benefits of immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression overall survival benefit in many types cancer. With advances our knowledge about microenvironment, progress has been made development small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, checkpoints, oncogenic signaling, metabolic cytokine/chemokine immune-related kinases have extensively investigated. Monotherapy immunotherapeutic their combinations with other antitumor modalities are under active investigations to overcome tolerance circumvent inhibitor resistance. Here, we review latest agents immunotherapy defined pathways highlighting recent investigations.

Language: Английский

Citations

23
An in-situ peptide-antibody self-assembly to block CD47 and CD24 signaling enhances macrophage-mediated phagocytosis and anti-tumor immune responses DOI Creative Commons

Weiqi Zhang,

Yinghua Zeng,

Qiuqun Xiao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 6, 2024

Abstract Targeted immunomodulation for reactivating innate cells, especially macrophages, holds great promise to complement current adaptive immunotherapy. Nevertheless, there is still a lack of high-performance therapeutics blocking macrophage phagocytosis checkpoint inhibitors in solid tumors. Herein, peptide-antibody combo-supramolecular situ assembled CD47 and CD24 bi-target inhibitor (PAC-SABI) described, which undergoes biomimetic surface propagation on cancer cell membranes through ligand-receptor binding enzyme-triggered reactions. By simultaneously signaling, PAC-SABI enhances the phagocytic ability macrophages vitro vivo, promoting anti-tumor responses breast pancreatic mouse models. Moreover, building foundation PAC-SABI-induced repolarization increased CD8 + T tumor infiltration, sequential anti-PD-1 therapy further suppresses 4T1 progression, prolonging survival rate. The vivo construction PAC-SABI-based nano-architectonics provides an efficient platform bridging immunity maximize therapeutic potency.

Language: Английский

Citations

13
Targets of tumor microenvironment for potential drug development DOI Creative Commons
Ling Zhang, Ziruoyu Wang,

Kailu Liu

et al.

MedComm – Oncology, Journal Year: 2024, Volume and Issue: 3(1)

Published: March 1, 2024

Abstract The tumor microenvironment (TME) is the ecosystem surrounding a tumor, which usually consists of nontumoral cells or components, and molecules they produce release. frequent continuous interplay between TME strongly affects development, disease progression, metastasis, responses to therapeutic interventions. As hub potential targets, has gained appreciable momentum in cancer research. Here we systematically review progress targeting as strategy develop novel antitumor drugs from immunological, stromal extracellular matrix components TME, shedding light on its complex synergies with cells. This exploration highlights transformative these elements hold refining treatment approaches. thorough examination not only accentuates TME's multifaceted nature but also positions it formidable avenue for propelling forward paradigms therapy. aims foster deeper understanding role oncogenesis exploitation advancing targeted, efficacious treatments, marking significant stride realm

Language: Английский

Citations

11
Eosinophil‐Activating Semiconducting Polymer Nanoparticles for Cancer Photo‐Immunotherapy DOI
Chi Zhang, Jingsheng Huang,

Mengke Xu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(30)

Published: May 3, 2024

Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted outcome cancer immunotherapies. We herein report an eosinophil-activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, reinvigorate T-cell immunity for activated photo-immunotherapy. SPNe comprises amphiphilic a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via

Language: Английский

Citations

11
Small-molecule-based targeted therapy in liver cancer DOI
Ming Yue, Yanqiu Gong,

Xuewen Fu

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(10), P. 3260 - 3287

Published: Aug. 8, 2024

Language: Английский

Citations

11
LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer DOI
Hansen Lin, Liangmin Fu, Xinwei Zhou

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216807 - 216807

Published: March 8, 2024

Language: Английский

Citations

10
Rising Star in Immunotherapy: Development and Therapeutic Potential of Small-Molecule Inhibitors Targeting Casitas B Cell Lymphoma-b (Cbl-b) DOI

Lixin Zhou,

Jiamei Yang,

Kuojun Zhang

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(2), P. 816 - 837

Published: Jan. 5, 2024

Casitas B cell lymphoma-b (Cbl-b) is a vital negative regulator of TCR and BCR signaling pathways, playing significant role in setting an appropriate threshold for the activation T cells controlling tolerance peripheral via variety mechanisms. Overexpression Cbl-b leads to immune hyporesponsiveness cells. Conversely, deficiency results markedly increased production IL-2, even lack CD28 costimulation vitro. And Cbl-b–/– mice spontaneously reject multifarious cancers. Therefore, may be associated with immune-mediated diseases, blocking could considered as new antitumor immunotherapy strategy. In this review, possible regulatory mechanisms biological potential are summarized. Besides, roles diseases comprehensively discussed, emphasis on immune-oncology agents preclinical stage clinical trials.

Language: Английский

Citations

9