The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 611 - 611

Published: Jan. 31, 2024

Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head neck cancers. The foundation this therapeutic approach lies immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy impeding neoplastic progression these tumours, their use may give rise to substantial toxicity, notably gastrointestinal domain, where ICI colitis constitutes significant aspect. optimal positioning Janus kinase (JAK)-signal transducer activator transcription (STAT) pathway management remains unclear. Numerous reports highlighted notable improvements through application pan-JAK-STAT inhibitors, with tofacitinib, particular, reporting evident clinical remission colitis. precise mechanism by which JAK-STAT impact pathogenetic process inadequately understood. However, there is speculation regarding potential role modulating memory resident CD8+ T lymphocytes. elucidation requires further extensive robust evidence, ongoing JAK-STAT-based trials are anticipated contribute valuable insights.

Language: Английский

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Exploring the resistance mechanism of triple-negative breast cancer to paclitaxel through the scRNA-seq analysis

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(1), P. e0297260 - e0297260

Published: Jan. 16, 2024

Background The triple negative breast cancer (TNBC) is the most malignant subtype of with high aggressiveness. Although paclitaxel-based chemotherapy scenario present mainstay in TNBC treatment, paclitaxel resistance still a striking obstacle for cure. So it imperative to probe new therapeutic targets through illustrating mechanisms underlying chemoresistance. Methods Single cell RNA sequencing (scRNA-seq) data cells treated at different points were downloaded from Gene Expression Omnibus (GEO) database. Seurat R package was used filter and integrate scRNA-seq expression matrix. Cells further clustered by FindClusters function, gene marker each subset defined FindAllMarkers function. Then, hallmark score calculated AUCell package, biological function highly expressed interest genes analyzed DAVID Subsequently, we performed pseudotime analysis explore change patterns drug SCENIC identify key transcription factors (TFs). Finally, inhibitors which also CTD Results We finally obtained 6 subsets 2798 cells, marked as AKR1C3+, WNT7A+, FAM72B+, RERG+, IDO1+ HEY1+HCC1143 subsets, among HEY1+ proportions increased increasing treatment time, then regarded subsets. Hallmark showed that these associated inflammatory response, virus interferon response activation. In addition, regulatory networks (GRNs) indicated 3 TFs (STAT1, CEBPB IRF7) played vital role promoting development, five common targeted potential combination therapies identified. Conclusion this study, identified relevant IFs their inhibitors, offers essential molecular basis beneficial guidance clinical therapy.

Language: Английский

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Chemo-immunotherapy by nanoliposomal epacadostat and docetaxel combination to IDO1 inhibition and tumor microenvironment suppression

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 137, P. 112437 - 112437

Published: June 12, 2024

Language: Английский

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Indoleamine 2,3-Dioxygenase (IDO) Activity: A Perspective Biomarker for Laboratory Determination in Tumor Immunotherapy

Biomedicines, Journal Year: 2023, Volume and Issue: 11(7), P. 1988 - 1988

Published: July 13, 2023

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme involved in catalyzing the conversion of tryptophan (Trp) into kynurenine (Kyn) at first rate-limiting step pathway L-tryptophan metabolism. It has been found to be several biological functions such as aging, immune microorganism, neurodegenerative and infectious diseases, cancer. IDO1 plays an important role tolerance by depleting tumor microenvironment inhibiting proliferation effector T cells, which makes it emerging biomarker for cancer immunotherapy. Therefore, research development inhibitors are great importance therapy. Of interest, IDO activity assays value screening evaluation inhibitors. Herein, we mainly review IDO1, regulation, key signaling molecules response pathway, clinical trials. Furthermore, this provides comprehensive overview and, particular, discussion currently available use human blood. We believe that promising escape laboratory

Language: Английский

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Matrigel implants embedded with IDVCs (IDO1-dependent vascularizing cells) to study inflammatory neovascularization

Methods in cell biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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IDO1 improves postischemic neovascularization in aged mice by boosting endothelial NAD+ de novo synthesis and curbing endothelial senescence

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103695 - 103695

Published: May 1, 2025

Language: Английский

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A peripheral blood mononuclear cell-based in vitro model: A tool to explore indoleamine 2, 3-dioxygenase-1 (IDO1)

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 968, P. 176420 - 176420

Published: Feb. 16, 2024

Proinflammatory cytokines powerfully induce the rate-limiting enzyme indoleamine 2, 3-dioxygenase-1 (IDO-1) in dendritic cells (DCs) and monocytes, it converts tryptophan (Trp) into L-kynurenine (KYN), along kynurenine pathway (KP). This mechanism represents a crucial innate immunity regulator that can modulate T cells. work explores role of IDO1 lymphocyte proliferation within specific pro-inflammatory milieu.

Language: Английский

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Remodeling the Inflammatory and Immunosuppressive Tumor Microenvironment for Enhancing Antiangiogenic Gene Therapy of Colorectal Cancer

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

Abstract Fusobacterium nucleatum ( Fn ), as an intestinal pathogenic bacterium, is closely related to the occurrence, progression, and limited therapeutic efficacy of colorectal cancer (CRC). The presence within CRC communities induces inflammatory immunosuppressive microenvironment while promoting new vessel formation. Therefore, developing novel methods efficiently eliminate enhance outcomes against ‐associated great significance. Herein, a nanosystem named AFGTs‐PEG , which integrates antimicrobial agent lauric acid (LA), antiangiogenic gene (sFlt‐1), targeted polymer (OEI‐LA/PBA, OLP), DSPE‐mPEG, boost therapy ‐infected CRC, developed. sFlt‐1 delivered cells through lysosome escape, remarkably inhibiting formation at site ultimately leading cell death. In principle, LA used its biofilms, remodel by restraining generation factors preventing polarization M1 into M2 macrophages, thereby mitigating adverse effects on therapy. This study holds promise for treatment bacteria‐colonized tumors.

Language: Английский

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Association between AHR Expression and Immune Dysregulation in Pancreatic Ductal Adenocarcinoma: Insights from Comprehensive Immune Profiling of Peripheral Blood Mononuclear Cells

Cancers, Journal Year: 2023, Volume and Issue: 15(18), P. 4639 - 4639

Published: Sept. 19, 2023

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), has an immune suppressive environment that allows tumour cells to evade the system. The aryl-hydrocarbon receptor (AHR) is a transcription factor can be activated by certain exo/endo ligands, including kynurenine (KYN) and other tryptophan metabolites. Once activated, AHR regulates expression of various genes involved in responses inflammation. Previous studies have shown activation PDAC both pro-tumorigenic anti-tumorigenic effects, depending on context. It promote growth evasion suppressing anti-tumour or induce effects enhancing cell function. In this study involving 30 patients healthy individuals, peripheral blood samples were analysed. categorized into Low (12 patients) High/Medium (18 groups based gene mononuclear (PBMCs). group showed distinct characteristics, increased levels immune-suppressive proteins such as PDL1, well alterations lymphocyte monocyte subtypes. Functional assays demonstrated changes phagocytosis, nitric oxide production, cytokines IL-1, IL-6, IL-10. These findings indicate AHR’s level crucial role dysregulation could potential target for early diagnostics personalised therapeutics.

Language: Английский

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Gut-brain connections in neurodegenerative disease: immunotherapeutic targeting of Bin1 in inflammatory bowel disease and Alzheimer’s disease

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: July 13, 2023

Longer lifespan produces risks of age-associated neurodegenerative disorders such as Alzheimer’s disease (AD), which is characterized by declines in memory and cognitive function. The pathogenic causes AD are thought to reflect a progressive aggregation the brain amyloid plaques composed beta-amyloid (Aß) peptides neurofibrillary tangles phosphorylated tau protein. Recently, long-standing investigations Aß hypothesis gained support via passive immunotherapy targeting soluble Tau-targeting approaches using antibodies also being pursued therapeutic approach AD. In genome-wide association studies, modifier gene Bin1 has been identified top risk factor for late-onset human populations, with recent studies suggesting that binds influences its extracellular deposition. Interestingly, before emerges brain, levels rise colon, where Bin1—a tissue barrier function inflammation—acts promote inflammatory bowel (IBD). This connection provocative given clinical evidence gut-brain communication disorders, including this review, we discuss Bin1-targeting developed our laboratory treat IBD may offer strategy indirectly reduce deposition limit onset or progression.

Language: Английский

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