Cytokine & Growth Factor Reviews最新文献

{"title":"Emerging involvement of CXCL13 in cancer development and progression","authors":"Dimitrios G. Argyris ,&nbsp;Lillian Johnson ,&nbsp;Thomas Hägglöf ,&nbsp;Panagiota S. Filippou ,&nbsp;George S. Karagiannis","doi":"10.1016/j.cytogfr.2025.12.005","DOIUrl":"10.1016/j.cytogfr.2025.12.005","url":null,"abstract":"<div><div>CXCL13, a chemokine originally identified for its role in B-cell trafficking, signals through the G-protein-coupled receptor CXCR5, to organize germinal centers and maintain immune architecture in secondary lymphoid organs. Beyond its physiological functions, accumulating evidence implicates the CXCL13-CXCR5 axis in the reciprocal regulation of inflammation and cancer. In this review, we outline our current understanding of its molecular organization, signaling properties, and regulatory feedback loops that fine-tune receptor activity. We further examine how CXCL13-CXCR5 signaling contributes to aquisition of cancer hallmarks, mainly through angiogenesis, epithelial-mesenchymal transition, metastatic niche conditioning, and the formation of tertiary lymphoid structures that influence antitumor immunity. By integrating biochemical, structural, and immunological insights, this review highlights the CXCL13-CXCR5 axis as a critical interface between lymphoid neogenesis and tumor evolution, and as a potential target for therapeutic modulation in cancer.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"87 ","pages":"Pages 73-88"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cytokine–skin barrier axis in health and disease","authors":"Maria Victoria Souto-Silva ,&nbsp;Elizabete Cristina Iseke Bispo ,&nbsp;Nakaly Natiely de Oliveira ,&nbsp;Robert Pogue ,&nbsp;Alessandra Zonari ,&nbsp;Felipe Saldanha-Araujo ,&nbsp;Juliana Lott Carvalho","doi":"10.1016/j.cytogfr.2025.12.009","DOIUrl":"10.1016/j.cytogfr.2025.12.009","url":null,"abstract":"<div><div>The skin barrier functions as both a structural defense and an immunological interface that integrates environmental, microbial, and systemic signals. Its disruption predisposes to cutaneous inflammation and contributes to systemic immune dysregulation. In this review, we provide an integrated analysis of how cytokine signaling regulates skin barrier integrity, highlighting both mechanistic insights and clinical implications across health and disease. We first revisit the architecture of the skin barrier and describe common insults that compromise its function, and the mechanisms by which these activate canonical signalling pathways—NF-κB, MAPK, JAK-STAT, and PI3K/Akt/mTOR—leading to the release of cytokines from keratinocytes and immune cells. Particular attention is given to cytokine families with direct relevance for epidermal physiology: IL-1 and IL-17 in antimicrobial defense and hyperinflammation; IL-20, IL-31, and type 2 cytokines in keratinocyte proliferation, differentiation, and barrier protein suppression; and TNF and interferons in amplifying inflammation and tissue injury. We also discuss how these cytokine networks drive systemic manifestations, linking skin barrier dysfunction to atopic dermatitis (AD), psoriasis, inflammaging, and metabolic disorders. Finally, we review therapeutic approaches that target cytokine signaling or restore barrier integrity, ranging from emollients and microbiome-based strategies to biologics and JAK inhibitors. By systematically reviewing the cytokine–barrier axis, this work highlights how modulation of cytokine signaling represents a promising avenue for clinical and preventive interventions in dermatology and systemic health.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"87 ","pages":"Pages 113-123"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination therapy strategies targeting glypican-3 in hepatocellular carcinoma: A comprehensive review","authors":"Sina Nabiyi ,&nbsp;Mohammad Heiat ,&nbsp;Ehsan Rezaei","doi":"10.1016/j.cytogfr.2025.12.006","DOIUrl":"10.1016/j.cytogfr.2025.12.006","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Advanced disease often proves resistant to conventional therapies, thereby driving the intensive search for targeted therapies. Glypican-3 (GPC3), a well-validated, signature tumor antigen in HCC, has emerged as an attractive therapeutic target with high potential for precision oncology. Current research strategies for developing novel GPC3-targeted therapeutics are highly diverse, encompassing cellular immunotherapies (e.g., CAR-T and NK cell therapies), antibody-based agents, immunotoxins, peptide vaccines, gene therapies, and nanoparticle-mediated drug delivery systems. Despite promising preclinical and clinical developments, the clinical translation of GPC3-targeted therapies is limited by challenges such as inadequate tumor penetration, immunosuppressive tumor microenvironment, and heterogeneous antigen expression. Consequently, recent research has increasingly shifted toward combination strategies. A growing body of experimental and early clinical data indicates that GPC3-targeted agents synergize effectively with a broad range of co-treatments, including immune checkpoint inhibitors, antiangiogenics, immune modulators, tyrosine kinase inhibitors, radiotherapy, chemotherapy, and local therapies to enhance antitumoral efficacy. In this review, we examine the potential of these multimodal strategies to develop more effective therapeutic approaches for HCC. Future studies should therefore focus on optimizing these combination regimens by incorporating personalized treatment strategies to achieve durable clinical outcomes.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"87 ","pages":"Pages 89-101"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial immunomodulatory structures as determinants of the maternal immune response and autism risk","authors":"Isaac S.B. Russell ,&nbsp;Melissa L. Perreault","doi":"10.1016/j.cytogfr.2025.12.010","DOIUrl":"10.1016/j.cytogfr.2025.12.010","url":null,"abstract":"<div><div>Autism is a group of neurodevelopmental conditions that have shown increasing prevalence over the last several decades. Despite being largely idiopathic in origin, numerous genetic and environmental risk factors have been identified. One of the leading environmental risk factors for autism is maternal immune activation (MIA) following infection. The impact of bacterial infection on MIA and neurodevelopmental outcomes has been widely studied though the specific causal underpinnings that directly influence autism risk remains elusive. In preclinical research, bacterial-derived lipopolysaccharide (LPS) is most often used to model bacterial infection and drive immune responses and autism-like outcomes. However, pathogenic structural determinants of the specific MIA response are rarely considered. Male and female fetuses also have distinct immune responses to MIA, which have been linked to sex-specific alterations in mitochondrial dysfunction and placental barrier disruption resulting in distinct behavioural characteristics. This review will discuss the known clinical and preclinical research on the impact of infection on MIA and neurodevelopmental outcomes, emphasizing the key role of bacterial structural factors. Here, we put forth that it is not only the severity, timing, and physical location of a bacterial infection that is important. Rather it is more nuanced, involving variations in key pathogenic immunostimulatory structures that, in turn, lead to a diversity of immune response phenotypes in both the mother and offspring, and distinct alterations in placental barrier integrity.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"87 ","pages":"Pages 128-139"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post COVID-19 pandemic Inflammatory Insights into Cancer: Consequences for immunotherapy","authors":"Carla Eksteen ,&nbsp;Lé-chandré Asja ,&nbsp;Atarah Rass ,&nbsp;Johann Riedemann ,&nbsp;Anna-Mart Engelbrecht","doi":"10.1016/j.cytogfr.2025.12.002","DOIUrl":"10.1016/j.cytogfr.2025.12.002","url":null,"abstract":"<div><div>The COVID-19 pandemic has reshaped the landscape of global health, revealing novel interactions between infectious diseases and chronic conditions such as cancer. Beyond acute infection, growing evidence suggests that persistent exposure to SARS-CoV-2 spike protein, whether through infection or vaccination, may sustain inflammatory pathways that contribute to tumour progression and immune modulation. This review explores the overlap between post-COVID inflammation, particularly in Long-COVID syndromes and the tumour microenvironment (TME), focusing on key mediators such as IL-6, TNF-α, IL-1β, and NF-κB. We revisit the concept of the cytokine storm in the context of persistent inflammation, spike protein immunogenicity and immune exhaustion, proposing a model in which chronic inflammatory signalling may disrupt tumour immune surveillance, reawaken dormant cancer cells and compromise the efficacy of immunotherapies. Comparative analysis with other cancer types highlights shared pathways of oncogenic inflammation. Lastly, we outline emerging therapeutic strategies to mitigate these effects, including cytokine-targeted interventions and immunomodulatory screening in post-COVID cancer patients. These post-pandemic insights call for urgent translational research to ensure effective and safe cancer immunotherapy in the evolving inflammatory landscape.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"87 ","pages":"Pages 10-18"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferons as therapeutic orchestrators of cancer stem cell plasticity and therapy response","authors":"Deepakshi Kasat ,&nbsp;Sophia Hidalgo ,&nbsp;Lu Wang,&nbsp;Jack D Bui,&nbsp;Magalie Dosset","doi":"10.1016/j.cytogfr.2025.12.008","DOIUrl":"10.1016/j.cytogfr.2025.12.008","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) represent a small but critical subset of tumor cells characterized by their inherent self-renewal ability, differentiation potential, and resistance to cancer therapies. Their capacity to reversibly transition between a stem-like and differentiated state, together with their ability to enter into quiescence, are key determinants of their contribution to tumor initiation, tumor progression, metastasis, and cancer recurrence. Among the various factors in the tumor microenvironment, increasing evidence suggests that interferons (IFNs) are key extrinsic modulators of CSC fate. Although type I (IFN-α/β) and type II (IFN-γ) IFNs have long been recognized for their antitumor properties, recent studies indicate that IFN-signaling may also facilitate CSC induction and maintenance. In this review, we summarize and critically assess our current understanding of the complex roles of IFNs in governing CSC survival, plasticity, and immunogenicity. We discuss how IFN-signaling thresholds, signaling duration, and intrinsic CSC regulatory networks determine whether IFNs suppress CSCs or instead reinforce stemness. By bridging mechanistic insights with therapeutic potential and clinical outcomes, we highlight emerging opportunities to exploit IFN pathways for improved biomarkers and therapeutic strategies to overcome CSC-driven resistance.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"87 ","pages":"Pages 102-112"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat shock protein 70 (Hsp70) as a target for advancing immunotherapy in solid tumors","authors":"Khouloud Hachani ,&nbsp;Mohamad Ghanem ,&nbsp;A. Graham Pockley ,&nbsp;Barbara Wollenberg ,&nbsp;Ali Bashiri Dezfouli ,&nbsp;Gabriele Multhoff","doi":"10.1016/j.cytogfr.2025.09.002","DOIUrl":"10.1016/j.cytogfr.2025.09.002","url":null,"abstract":"<div><div>Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that maintains protein homeostasis (proteostasis) under stress conditions. In cancer, Hsp70 is frequently overexpressed, where it contributes to hallmark features of malignancy by stabilizing oncogenic proteins, suppressing apoptosis, and promoting invasion and immune evasion. Beyond its intracellular functions, Hsp70 is aberrantly presented on the plasma membrane of a broad range of solid tumor cells and actively released into the extracellular space, either in soluble form or encapsulated within extracellular lipid microvesicles with biophysical characteristics of exosomes, supporting tumor microenvironment remodeling and immune modulation. The selective surface expression of Hsp70 on tumor cells, but not healthy tissues, defines it as a tumor-associated antigen (TAA) and an accessible target for immunotherapy. Leveraging this unique feature, several therapeutic approaches have been developed addressing membrane Hsp70 on tumor cells, including small molecule inhibitors, peptide-mediated activation of natural killer (NK) cells, monoclonal antibodies, fusion vaccines, and chimeric antigen receptor (CAR)-engineered immune cells. In parallel, extracellular Hsp70 in the blood is emerging as a promising liquid biomarker for patient stratification and treatment monitoring in cancer patients. This review outlines the context-dependent roles of Hsp70 in cancer and critically evaluates its translational potential as both a therapeutic target and diagnostic marker in solid tumors. We also discuss advances in detection technologies, findings from early-phase clinical trials, and persistent challenges such as off-target effects, tumor heterogeneity, and achieving effective and selective targeting.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 83-95"},"PeriodicalIF":11.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the NLRP3 inflammasome in sepsis: Molecular mechanisms and therapeutic strategies","authors":"Yuhui Ma,&nbsp;Jialei Meng,&nbsp;Fangyuan Sun,&nbsp;Ming Lei","doi":"10.1016/j.cytogfr.2025.09.006","DOIUrl":"10.1016/j.cytogfr.2025.09.006","url":null,"abstract":"<div><div>Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host response to infection, with immune homeostasis imbalance at the core of its pathological mechanism. The NACHT, leucin-rich repeat (LRR) and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome, as an innate immune sensor, plays a critical role in the development and progression of sepsis. Upon activation, the NLRP3 inflammasome triggers caspase-1 activation, which mediates the maturation and release of IL-1β and IL-18, as well as pyroptosis. Studies have demonstrated that inhibiting NLRP3 inflammasome activation can significantly alleviate sepsis-associated systemic inflammatory responses and improve prognosis. This review systematically elucidates the pathophysiological mechanisms of sepsis, the activation mechanisms of the NLRP3 inflammasome, and its dual regulatory role in sepsis progression. Moderate NLRP3 activation aids in pathogen clearance, whereas excessive activation exacerbates cytokine storms, leading to multi-organ failure. Finally, we summarize the latest research progress on NLRP3 inhibitors currently in clinical trial stages. This article aims to provide insights for the development of NLRP3-targeted therapeutic drugs for sepsis.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 57-70"},"PeriodicalIF":11.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of cytokine-based immunotherapy approaches in gastrointestinal cancers","authors":"Rafik ElBeblawy ,&nbsp;Midhun Malla ,&nbsp;Mehmet Akce","doi":"10.1016/j.cytogfr.2025.10.005","DOIUrl":"10.1016/j.cytogfr.2025.10.005","url":null,"abstract":"<div><div>Gastrointestinal (GI) cancers are among the most common leading causes of cancer-related mortality globally and they are the leading cause of cancer-related mortality in the US. Immune checkpoint inhibitor (ICI)-based therapies altered treatment paradigm in several tumor types including GI cancers. Despite encouraging results in select GI cancers, response rate is low, and treatment resistance poses a challenge in clinical practice. Cytokines are soluble mediators that regulate immune responses and can either promote or inhibit tumor growth depending on their impact on the tumor microenvironment (TME). In GI cancers, chronic inflammation driven by cytokines such as IL-6, IL-10, TNF-α, and TGF-β facilitates immune evasion and tumor progression. Cytokines contribute to the histopathogenesis of GI cancers by driving chronic inflammation, promoting epithelial-to-mesenchymal transition, and remodeling the TME to favor immunosuppression and angiogenesis. This cytokine-mediated landscape not only supports tumor initiation and progression but also influences systemic therapy outcomes by fostering resistance to chemotherapy and dampening responsiveness to immunotherapy. Integrating cytokine-targeted strategies with ICIs may enhance antitumor immunity by reversing T-cell exhaustion, improving effector T cell infiltration and function, and reprogramming the tumor milieu toward a pro-inflammatory, immune-permissive state potentially overcoming resistance and improving clinical efficacy.</div><div>While ICIs have attracted most of the research interest in the past decade, cytokine-based therapy is another frontier to be utilized as either a therapeutic agent or a target to regulate cancer immunogenicity. In this review we aim to present a comprehensive discussion about relevant cytokines in GI cancers and explain mechanism of cytokines in immune regulation, discuss therapeutic potential of different cytokines, interleukins, interferons, tumor growth factors and their clinical application in recent clinical trials either alone or combined with other immunotherapeutic agents in GI cancers. Additionally, we discuss the potential limitations and challenges of cytokine-based immunotherapy in GI cancers.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 149-166"},"PeriodicalIF":11.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arteriolar angiogenesis: implications in anti-angiogenic immunotherapy for pancreatic cancers","authors":"Adam W. Beck,&nbsp;Herbert Chen,&nbsp;Bin Ren","doi":"10.1016/j.cytogfr.2025.10.002","DOIUrl":"10.1016/j.cytogfr.2025.10.002","url":null,"abstract":"<div><div>Angiogenesis, the newly formed blood vessels from preexistent ones, is essential for the progression and potential resolution of diseases. Here we introduce a view of arteriolar angiogenesis (the growth of new small arteries), and define a concept that molecular signaling balance between pro- and anti-angiogenic signaling determines angiogenic phenotype. We discuss VEGF and CXCL12 signaling pathways in vascular endothelial cells essential for arteriolar angiogenesis, which is potentially regulated by PKD1-mediated Notch1-CD36 signaling, emphasizing the function of arteriolar angiogenesis as a vascular niche/microenvironment under pathological conditions. We delineate implications of arteriolar angiogenesis in cancer stem cell development and anti-angiogenic immunotherapeutic strategies, highlighting anti-angiogenic strategy in combination with immune checkpoint blockade in pancreatic cancers. In summary, this review article seeks to develop the concept of arteriolar angiogenesis and yield insights into developing novel vascular targeting and immune therapies to cure cancers and cardiovascular and neurovascular diseases manifested with abnormal angiogenesis.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 96-107"},"PeriodicalIF":11.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}