Targeting cytokine and chemokine signaling pathways for cancer therapy

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

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Roles of Interferon Regulatory Factor 1 in Tumor Progression and Regression: Two Sides of a Coin

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2153 - 2153

Published: Feb. 10, 2024

IRF1 is a transcription factor well known for its role in IFN signaling. Although was initially identified involvement inflammatory processes, there now evidence that it provides function carcinogenesis as well. has been shown to affect several important antitumor mechanisms, such induction of apoptosis, cell cycle arrest, remodeling tumor immune microenvironment, suppression telomerase activity, angiogenesis and others. Nevertheless, the opposite effects on growth have also demonstrated. In particular, “immune checkpoint” molecule PD-L1, which responsible evasion, major transcriptional regulator. These other properties IRF1, including proposed association with response resistance immunotherapy chemotherapeutic drugs, make promising object further research. Numerous mechanisms regulation cancer identified, genetic, epigenetic, transcriptional, post-transcriptional, post-translational although their significance progression remains be explored. This review will focus established tumor-suppressive tumor-promoting functions molecular various cancers.

Language: Английский

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Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 30, 2024

Abstract Although immune checkpoint-based cancer immunotherapy has shown significant efficacy in various cancers, resistance still limits its therapeutic effects. Ubiquitination modification is a mechanism that adds different types of ubiquitin chains to proteins, mediating protein degradation or altering their function, thereby affecting cellular signal transduction. Increasing evidence suggests ubiquitination plays crucial role regulating the mechanisms immunotherapy. Drugs targeting pathways have been inhibit tumor progression enhance This review elaborates on by which cells, and microenvironment mediate details how regulates these mechanisms, providing foundation for enhancing intervening modification.

Language: Английский

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Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Nov. 7, 2024

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as complex cytokine storm. This hyperactive response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements its treatment. The storm plays crucial role treatment of HLH. Investigating detailed mechanisms behind storms offers insights into targeted therapeutic approaches, potentially aiding early intervention improving clinical outcome patients. To date, only one therapy, emapalumab targeting interferon-γ, that gained approval for primary review aims summarize current advances, emerging therapeutics underlying HLH, highlighting newly discovered targets involved storms, which are expected drive development novel treatments offer fresh perspectives future studies. Besides, multi-targeted combination therapy may be essential disease control, but further trials required determine optimal mode

Language: Английский

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Immunotherapeutic potentials of carnosol against lipopolysaccharides-induced acute inflammatory reactions in White Swiss albino mice

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: 47(1), P. 101 - 111

Published: Jan. 2, 2025

Background and objective: Septic shock involves severe systemic inflammatory reaction toward various invading species, such as microorganisms microbial toxins. Such a response is complicated characterized being dynamic time-dependent phenomenon. During this response, significant amount of pro-inflammatory cytokines may be produced, causing rapid death rate in septic victims occasionally leading to apoptosis immune cells within the first hours reaction. In order ameliorate reaction, intraperitoneal carnosol was studied against lipopolysaccharide (LPS) induced acute Swiss albino mice.

Language: Английский

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Identification of three subtypes of thyroid cancer based on IFN-γ-related genes to reveal their prognostic characteristics

Langenbeck s Archives of Surgery, Journal Year: 2025, Volume and Issue: 410(1)

Published: Feb. 14, 2025

Thyroid cancer is one of the deadliest malignancies. Increasing evidence suggests that interferon-γ (IFN-γ) plays an important role in anti-tumor immunity and its treatment. However, effectiveness classifying, predicting prognosis, immunotherapy for thyroid based on IFN-γ-related genes has not been discovered. We used Gene Set Enrichment Analysis (GSEA) database to obtain classified patients from The Cancer Genome Atlas (TCGA). systematically explored differences among various subtypes multiple perspectives, such as Kaplan-Meier survival analysis, tumor mutation immune enrichment drug sensitivity analysis. Finally, we screened some potential drugs suitable each population. Through clustering obtained three with different gene expression levels. analysis results showed significant these subtypes. In addition, found BRAF, TTN, TG were top highest frequency subtypes, which may be related their prognosis. Cluster 1 cluster 2 two greatest difference cell infiltration levels, differentially expressed mainly enriched immune-related biological processes or signaling pathways leukocyte-mediated immunity, regulation T activation, chemokine pathway. Eighteen compounds Cyclopamine, Erlotinib, FH535, Imatinib, A-770,041 selected therapeutic this study, varied. Based bioinformatics discovered a new classification method IFN-γ genes, could divide into populations characteristics. Different had patterns, candidate drugs.

Language: Английский

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Primary and Acquired Resistance to Immunotherapy with Checkpoint Inhibitors in NSCLC: From Bedside to Bench and Back

BioDrugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Immunotherapy with checkpoint inhibitors has become the cornerstone of systemic treatment for non-oncogene addicted non-small-cell lung cancer. Despite its pivotal role, a significant proportion patients—approximately 70–85%—either exhibit primary resistance to PD-1 blockade or develop acquired following an initial benefit, even in combination chemotherapy and/or anti-CTLA-4 agents. The phenomenon and immunotherapy represents critical clinical challenge, largely based on our incomplete understanding mechanisms action immunotherapy, resulting lack accurate predictive biomarkers. Here, we review definitions explore proposed resistance, including those related tumor microenvironment, factors, intrinsic characteristics. We also discuss translational data adaptive changes within cells immune infiltrate exposure inhibitors. Lastly, offer comprehensive overview current emerging therapeutic strategies designed prevent counteract resistance.

Language: Английский

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Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli

Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

ABSTRACT Microglia are the primary resident immune cells of central nervous system (CNS) that respond to injury and infections. Being critical CNS homeostasis, microglia also have been shown contribute neurodegenerative diseases brain cancer. Hence, regarded as a potential therapeutic target in diseases, resulting an increased demand for reliable vitro models. Two human cell lines (HMC3 C20) being used multiple studies, however, knowledge their biological immunological characteristics remains limited. Our aim was identify compare changes these immortalised under normal physiological immunologically challenged conditions. Using high‐resolution quantitative mass spectrometry, we examined in‐depth proteomic profiles non‐stimulated LPS or IFN‐γ HMC3 C20 cells. findings reveal responded both treatments through upregulation immune, metabolic, antiviral pathways, while showed response associated with mitochondrial activities. Additionally, secretome analysis demonstrated release IL‐6 LPS, treatment resulted altered kynurenine pathway activity, highlighting distinct metabolic adaptations.

Language: Английский

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An Immunogenic Cell Death-Related Gene Signature Predicts the Prognosis and Immune Infiltration of Cervical Cancer

Cancer Informatics, Journal Year: 2025, Volume and Issue: 24

Published: Jan. 1, 2025

Objectives: Immunogenic cell death (ICD) has been demonstrated to play a critical role in the development and progression of malignant tumors by modulating anti-tumor immune response. However, its function cervical cancer (CC) remains largely unexplored. In this study, we aimed construct an ICD-related gene signature predict patient prognosis infiltration CC. Methods: The expression profiles clinical data CC were downloaded from Cancer Genome Alas (TCGA) Gene Expression Omnibus (GEO) datasets, serving as training testing groups, respectively. An was developed using LASSO-Cox model. levels associated genes evaluated single-cell data, lines, samples vitro. Results: Two ICD-associated subtypes (cluster 1 cluster 2) identified through consensus clustering. Patients classified into 2 higher exhibited more favorable prognosis. Subsequently, comprising 3 (IL1B, IFNG, FOXP3) established for Based on median risk score, patients both cohorts segregated high-risk low-risk groups. Further analyses indicated that estimated score functioned independent prognostic factor influenced abundance within tumor microenvironment. up-regulation further validated lines collected samples. Conclusion: summary, stratification based strong efficacy predicting infiltration, which also provides valuable new perspectives diagnosis

Language: Английский

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Clinical Characteristics Analysis of 30 Cases of Interferon-γ Autoantibody-Positive Patients with Concurrent Mycobacterial Infection: A 6-Year Retrospective Study

Infection and Drug Resistance, Journal Year: 2025, Volume and Issue: Volume 18, P. 1097 - 1110

Published: Feb. 1, 2025

This study aimed to investigate and elucidate the clinical characteristics, immune status, infection types patterns, treatment responses, disease progression in patients with positive anti-interferon-gamma (IFN-γ) autoantibodies combination Mycobacterium infections. We conducted a retrospective analysis of data from anti-IFN-γ concurrent Mycobacterial infections, including infections (MTB) non-tuberculous mycobacteria (NTM). The included cases treated at Fourth People's Hospital Nanning, Guangxi, 2018 2023. Data collected comprised symptoms, signs, laboratory test results, imaging findings, other relevant information. Patients were also followed up evaluate responses long-term therapeutic outcomes. A total 30 MTB NTM analyzed. majority presented common such as cough, sputum production, weight loss, extrapulmonary tuberculosis (TB), range opportunistic Laboratory studies revealed complex patterns various pathological changes. Treatment primarily involved targeted anti-infective therapy combined immunosupportive measures. However, frequent relapses side effects observed, resulting two deaths. Immune deficiency associated resembles immunosuppression seen advanced stages human immunodeficiency virus/acquired syndrome (HIV/AIDS), rendering highly susceptible These predominantly caused by NTM, Talaromyces marneffei (TM). represents novel that predisposes spectrum

Language: Английский

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