Cytokine & Growth Factor Reviews最新文献

Targeting the NLRP3 inflammasome in sepsis: Molecular mechanisms and therapeutic strategies NLRP3炎性体在脓毒症中的靶向作用：分子机制和治疗策略

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-10-01 DOI: 10.1016/j.cytogfr.2025.09.006

Yuhui Ma, Jialei Meng, Fangyuan Sun, Ming Lei

{"title":"Targeting the NLRP3 inflammasome in sepsis: Molecular mechanisms and therapeutic strategies","authors":"Yuhui Ma, Jialei Meng, Fangyuan Sun, 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":"2025-10-01","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}

引用次数: 0

Erratum to “TLR-Based therapeutic strategies for Hepatocellular carcinoma” [Cytokine Growth Factor Rev. Volume 85 2025 Pages 179–189] “基于tlr的肝细胞癌治疗策略”的勘误[细胞因子生长因子Rev.卷85 2025页179-189]

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-09-24 DOI: 10.1016/j.cytogfr.2025.09.005

Manoj Kumar Gupta , Ramakrishna Vadde

引用次数: 0

Designing immunity with cytokines: A logic-based framework for programmable CAR therapies 用细胞因子设计免疫：可编程CAR疗法的逻辑框架

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-09-18 DOI: 10.1016/j.cytogfr.2025.09.004

Saurabh Upadhyay, Kirti Upmanyu, Moustafa T. Gabr

{"title":"Designing immunity with cytokines: A logic-based framework for programmable CAR therapies","authors":"Saurabh Upadhyay, Kirti Upmanyu, Moustafa T. Gabr","doi":"10.1016/j.cytogfr.2025.09.004","DOIUrl":"10.1016/j.cytogfr.2025.09.004","url":null,"abstract":"<div><div>Adoptive cellular immunotherapy has transformed cancer care, with chimeric antigen receptor (CAR) T cells achieving unprecedented remission in hematologic malignancies. Yet solid tumor translation remains limited by antigen escape, hostile microenvironments, and life-threatening toxicities. Cytokines and chemokines are central to these barriers, shaping trafficking, persistence, and toxicity in ways that demand engineered solutions. This review introduces the first unified five-layer framework—Recognition, Navigation, Safety, Persistence, and Translation—that organizes CAR engineering through cytokine and chemokine logic. Innovations include dual-target and logic-gated CARs to counter heterogeneity, hypoxia- and chemokine-responsive circuits to enhance infiltration, inducible safety switches to mitigate IL-6/IL-1β–driven cytokine storm, and IL-7/IL-15 support to extend persistence. Beyond T cells, CAR logic is now ported into NK cells and macrophages, complementing adaptive memory with innate cytotoxicity and stromal remodeling, while iPSC-derived effectors offer scalable, standardized production. Together, these advances reframe cellular immunotherapy as a cytokine-guided, programmable immune ecosystem, providing a conceptual roadmap for therapies engineered not only for potency but also for safety, durability, and broad clinical integration.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 40-55"},"PeriodicalIF":11.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108362","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}

引用次数: 0

Wiring and rewiring PANoptosis: Molecular vulnerabilities for targeting inflammatory cell death in human disease PANoptosis：人类疾病中针对炎症细胞死亡的分子脆弱性。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-09-13 DOI: 10.1016/j.cytogfr.2025.09.003

Kirti Upmanyu , Saurabh Upadhyay

{"title":"Wiring and rewiring PANoptosis: Molecular vulnerabilities for targeting inflammatory cell death in human disease","authors":"Kirti Upmanyu , Saurabh Upadhyay","doi":"10.1016/j.cytogfr.2025.09.003","DOIUrl":"10.1016/j.cytogfr.2025.09.003","url":null,"abstract":"<div><div>PANoptosis represents a unified inflammatory cell death program that mechanistically integrates pyroptosis, apoptosis, and necroptosis through multiprotein complexes known as PANoptosomes. While prior models treated these death pathways as distinct, emerging evidence reveals their convergence through shared sensors, signaling adaptors, and executioners—allowing cells to bypass immune evasion strategies by pathogens or tumors. Despite its biological importance, a cohesive mechanistic framework for PANoptosis has remained elusive. In this review, we present a novel, sensor-specific dissection of PANoptosome architecture, detailing how distinct innate immune sensors—ZBP1, RIPK1, AIM2, and NLRP12 serve as organizing hubs for context-dependent activation of inflammatory cell death. We integrate this with a cross-pathway analysis of caspase-8, RIP kinases, and gasdermins, revealing PANoptosis as a highly adaptable logic circuit governing immune activation and cell fate. We further chart the dual roles of PANoptosis across disease contexts—highlighting its protective functions in infection and tumor suppression, as well as its detrimental consequences in cytokine storms, neurodegeneration, and multi-organ failure. By comparing sensor-driven outcomes across organs and disease states, we propose new therapeutic entry points for modulating PANoptotic signaling with precision. This review offers a mechanistically integrated and translationally focused roadmap to PANoptosis, establishing it as a master regulator of inflammatory cell death and a frontier for next-generation immune interventions.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 1-16"},"PeriodicalIF":11.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091309","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}

引用次数: 0

Myokines and osteokines in aging-related degenerative diseases: Regulatory networks in the muscle-bone-brain axis 衰老相关退行性疾病中的肌因子和骨因子：肌-骨-脑轴的调节网络。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-09-07 DOI: 10.1016/j.cytogfr.2025.09.001

Shang Gao , Nianhu Li , Lijie Qi , Xin Li , Jie Zhang , Zhaoqi Zhang , Zhaoyao Xu , Songlin Liang , Weiming Zhu , Wei Liu

引用次数: 0

Heat shock protein 70 (Hsp70) as a target for advancing immunotherapy in solid tumors. 热休克蛋白70 （Hsp70）作为推进实体瘤免疫治疗的靶点。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-09-06 DOI: 10.1016/j.cytogfr.2025.09.002

Khouloud Hachani, Mohamad Ghanem, A Graham Pockley, Barbara Wollenberg, Ali Bashiri Dezfouli, Gabriele Multhoff

{"title":"Heat shock protein 70 (Hsp70) as a target for advancing immunotherapy in solid tumors.","authors":"Khouloud Hachani, Mohamad Ghanem, A Graham Pockley, Barbara Wollenberg, Ali Bashiri Dezfouli, Gabriele Multhoff","doi":"10.1016/j.cytogfr.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2025.09.002","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-06","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}

引用次数: 0

From senescence to scarring: Exploring TGF-β signaling in cellular aging, fibrotic remodeling, and pulmonary fibrosis 从衰老到瘢痕形成：探索TGF-β信号在细胞衰老、纤维化重塑和肺纤维化中的作用。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-08-22 DOI: 10.1016/j.cytogfr.2025.08.003

Shivani Bhardwaj, Rohit Kumar Gautam, Sapana Kushwaha

{"title":"From senescence to scarring: Exploring TGF-β signaling in cellular aging, fibrotic remodeling, and pulmonary fibrosis","authors":"Shivani Bhardwaj, Rohit Kumar Gautam, Sapana Kushwaha","doi":"10.1016/j.cytogfr.2025.08.003","DOIUrl":"10.1016/j.cytogfr.2025.08.003","url":null,"abstract":"<div><div>Cellular senescence and the formation of fibrotic scarring are critical in the progression of chronic illnesses, such as pulmonary fibrosis (PF). In this context, the transforming growth factor-beta (TGF-β) pathway represents a central driver in orchestrating the pathological cascade. TGF-β governs cellular activities such as differentiation, apoptosis, and extracellular matrix (ECM) remodeling as a pleiotropic cytokine. In the lungs, dysregulated TGF-β signaling leads to cellular senescence and release of pro-inflammatory mediators, constituting the senescence-associated secretory phenotype (SASP). This reinforces a microenvironment conducive to fibroblast activation, prolonged myofibroblast retention, and accelerated aberrant ECM deposition, culminating in progressive tissue fibrosis. For instance, idiopathic pulmonary fibrosis (IPF) is marked by the buildup of senescent alveolar epithelial cells (AECs) that impair regular tissue repair and alter the microenvironment to promote fibrogenesis. TGF-β signaling is activated through SMAD-dependent (canonical) and SMAD-independent (non-canonical) pathways, each contributing to the persistence of activated fibroblasts, aberrant ECM accumulation, and irreversible tissue remodeling. The interdependence between senescence and TGF-β signaling perpetuates fibrotic injury and enhances susceptibility to future fibrotic insults. This review delves into understanding the molecular convergence of TGF-β signaling and cellular senescence in PF, highlighting key biomarkers and emerging therapeutic strategies. While several clinical trials evaluating TGF-β antagonists, small molecules, and cell-based therapies show considerable promise, challenges remain regarding their successful translation into effective, targeted treatments. Nevertheless, continued exploration of TGF-β’s multifaceted role in fibrosis and senescence offers hope for developing innovative therapies for PF and other chronic fibrotic diseases.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"86 ","pages":"Pages 29-39"},"PeriodicalIF":11.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945825","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}

引用次数: 0

TLR-based therapeutic strategies for hepatocellular carcinoma 基于tlr的肝细胞癌治疗策略。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-08-08 DOI: 10.1016/j.cytogfr.2025.08.002

Manoj Kumar Gupta , Ramakrishna Vadde

{"title":"TLR-based therapeutic strategies for hepatocellular carcinoma","authors":"Manoj Kumar Gupta , Ramakrishna Vadde","doi":"10.1016/j.cytogfr.2025.08.002","DOIUrl":"10.1016/j.cytogfr.2025.08.002","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related deaths worldwide. Chronic inflammation and immune dysregulation, often driven by viral infections or metabolic disorders, play a significant role in its pathogenesis. Toll-like receptors (TLRs), key components of innate immunity, have emerged as important regulators in the progression of liver disease and tumorigenesis. This review aims to evaluate the role of TLR signaling in the development, progression, and therapeutic potential of HCC. While TLRs are mainly found on immune cells, they are also functionally expressed in various human cancers, including HCC. TLRs, such as TLR4, can either promote or inhibit tumor progression, depending on the cellular context and microenvironment. TLR polymorphisms, including TLR1 rs5743551 and TLR4 rs1927914, are associated with inflammation, infection risk, and cancer recurrence. Although preclinical studies support the use of TLR agonists to enhance immunotherapy, their clinical translation remains limited due to inconsistent patient responses. This might be due to the diverse effects these agonists exert on various cell types within the tumor microenvironment. Future research should focus on patient-specific TLR profiles, the development of improved biomarkers, and the combination of therapies to optimize outcomes. Understanding the dual role of TLRs could lead to more precise and effective HCC treatments.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"85 ","pages":"Pages 179-189"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834493","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}

引用次数: 0

Neuro-endocrine-immune regulation of metabolic homeostasis 代谢稳态的神经内分泌免疫调节。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-08-05 DOI: 10.1016/j.cytogfr.2025.08.001

Cong Xie , Yuhan Lin , Cong Qi , Wei Wang , Yulian Yuan , Dechao Song , Zheng Wang , Hanjie Liu , Xingzhong Feng , Huijuan Gao

{"title":"Neuro-endocrine-immune regulation of metabolic homeostasis","authors":"Cong Xie , Yuhan Lin , Cong Qi , Wei Wang , Yulian Yuan , Dechao Song , Zheng Wang , Hanjie Liu , Xingzhong Feng , Huijuan Gao","doi":"10.1016/j.cytogfr.2025.08.001","DOIUrl":"10.1016/j.cytogfr.2025.08.001","url":null,"abstract":"<div><div>Metabolic homeostasis, essential for energy balance, is regulated by a highly integrated network involving the nervous, endocrine, and immune systems. While traditional models emphasized endocrine feedback mechanisms and autonomic nervous control, recent evidence reveals extensive cross-talk among these systems, forming a dynamic neuro-endocrine-immune network. The brain coordinates energy balance by integrating signals from peripheral organs, regulating appetite, metabolic rate, and nutrient utilization. Immune responses, particularly in obesity, contribute to metabolic dysfunction through chronic inflammation and cytokine cascades. This review synthesizes the cellular and molecular mechanisms underlying the neuro-endocrine-immune interactions that maintain glucose and energy homeostasis. We describe the functional roles of hypothalamic feeding circuits, peripheral autonomic pathways, adipokines, incretins, and immune cell subsets in metabolic tissues. We also highlight how chronic inflammation, neuroimmune signaling, and hormonal resistance contribute to homeostatic failure. Crucially, we examine emerging therapeutic strategies targeting obesity, type 2 diabetes, metabolic syndrome, and metabolic dysfunction-associated fatty liver disease—approaches that exert multi-system effects by precisely targeting key nodes within this regulatory triad. This integrative perspective not only offers novel paradigms for intervening in complex metabolic disorders but also heralds a future where decoding this network enables personalized medicine to transform clinical practice.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"85 ","pages":"Pages 165-178"},"PeriodicalIF":11.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858977","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}

引用次数: 0

Neuroprotective properties of ciliary neurotrophic factor in the retina for the treatment of macular telangiectasia type 2. 视网膜睫状体神经营养因子治疗2型黄斑毛细血管扩张的神经保护作用。

IF 11.8 2区医学

Cytokine & Growth Factor Reviews Pub Date : 2025-08-01 Epub Date: 2025-06-18 DOI: 10.1016/j.cytogfr.2025.06.005

Arne Nystuen, Eugene Gonzalez-Lopez, Konrad A Kauper, Kevin Eade, Thomas M Aaberg

{"title":"Neuroprotective properties of ciliary neurotrophic factor in the retina for the treatment of macular telangiectasia type 2.","authors":"Arne Nystuen, Eugene Gonzalez-Lopez, Konrad A Kauper, Kevin Eade, Thomas M Aaberg","doi":"10.1016/j.cytogfr.2025.06.005","DOIUrl":"10.1016/j.cytogfr.2025.06.005","url":null,"abstract":"<p><p>Neurotrophic factors are a family of proteins that promote the growth and survival of both developing and mature neurons. Extensive preclinical studies have demonstrated neuroprotective properties conferred by ciliary neurotrophic factor (CNTF) in a variety of neuron types across several species. Neuroprotection that CNTF confers slows or prevents neuron loss and appears to be agnostic to the nature of the neurodegenerative mutation or injury. However, translation of these studies to the clinic remains a challenge due in part to delivery barriers inherent to the central nervous system and the short half-life of CNTF. The molecular effect of CNTF delivered by a variety of strategies in model systems has been extensively studied in the neural retina. Long-term retinal neuroprotection has been documented using encapsulated cells that have been genetically modified to produce a stable source of CNTF. Clinical trials have shown that CNTF is well tolerated for use in the human retina. This review focuses on the mechanism of action of CNTF and its potential as a therapeutic agent in retinal disease, with a focus on macular telangiectasia type 2 where CNTF has shown efficacy in slowing the rate of ellipsoid zone loss.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":"12-19"},"PeriodicalIF":11.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494999","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}

引用次数: 0