IF 14.1

MedComm Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1002/mco2.70962

Linnan Li, Jinfeng Gao, Xiaoxue Zhang, Kunming Dai, Hao Cheng, Jianying Ma, Junbo Ge

{"title":"METTL3-Mediated N6-Methyladenosine Modification Activates the EGR1-ZBP1 Axis to Promote PANoptosis-Like Cardiomyocyte Death in Myocardial Ischemia-Reperfusion Injury.","authors":"Linnan Li, Jinfeng Gao, Xiaoxue Zhang, Kunming Dai, Hao Cheng, Jianying Ma, Junbo Ge","doi":"10.1002/mco2.70962","DOIUrl":"10.1002/mco2.70962","url":null,"abstract":"Myocardial ischemia-reperfusion (I/R) injury is a major cause of cardiac dysfunction, but the mechanisms linking metabolic stress to regulated cardiomyocyte death remain incompletely defined. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, is installed by the methyltransferase-like 3 (METTL3)-containing writer complex and regulates RNA fate. Here, we investigated whether METTL3-mediated m6A modification contributes to PANoptosis-like cardiomyocyte death during I/R injury. In mouse myocardial I/R and oxygen-glucose deprivation/reoxygenation (OGD/R) models, global m6A levels and METTL3 expression were markedly increased. Lactate accumulation was associated with p300-dependent H3K18 lactylation (H3K18la) enrichment at the Mettl3 promoter, suggesting a metabolic-epigenetic mechanism for METTL3 transcriptional upregulation. Functionally, METTL3 promoted PANoptosis-related death signaling, strengthened the association of ZBP1 with PANoptosis-related components, and aggravated infarction, adverse remodeling, and cardiac dysfunction, whereas METTL3 deletion or pharmacological inhibition with STM2457 was protective. Mechanistically, METTL3 enhanced m6A modification of Egr1 mRNA, thereby increasing EGR1 expression through YTHDF1-mediated translational regulation and IGF2BP2-mediated mRNA stabilization. EGR1 further activated Zbp1 transcription, and EGR1 restoration partially reversed the protective effects of METTL3 deficiency. These findings identify a lactate-H3K18la-METTL3-EGR1-ZBP1 axis that drives PANoptosis-like cardiomyocyte death and suggest METTL3 inhibition as a potential strategy against I/R-induced cardiac injury.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 9","pages":"e70962"},"PeriodicalIF":14.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases 利用自然杀伤细胞：从神经免疫学到中枢神经系统疾病的新疗法。

IF 14.1

MedComm Pub Date : 2026-09-21 DOI: 10.1002/mco2.70983

Kaihang Deng, Wai Po Chong

{"title":"Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases","authors":"Kaihang Deng, Wai Po Chong","doi":"10.1002/mco2.70983","DOIUrl":"10.1002/mco2.70983","url":null,"abstract":"Natural killer (NK) cells are innate lymphocytes that defend the host by directly killing virus-infected, stressed, and tumor cells. Their direct cytotoxic mechanisms include the release of cytotoxic granules, engagement of death receptor pathways, and mediation of antibody-dependent cellular cytotoxicity (ADCC). They can also eliminate targets indirectly via the secretion of proinflammatory cytokines. Importantly, recent studies show NK cells help limit autoimmunity by targeting autoreactive immune cells, highlighting their broader role in maintaining tissue homeostasis, including within the immune-privileged central nervous system (CNS). Both preclinical and clinical studies support the therapeutic potential of NK cell-based immunotherapies for neuroinflammatory, neurodegenerative, and neuro-oncologic diseases. A key challenge remains achieving sufficient specificity and efficacy within the CNS, which necessitates a more profound understanding of NK cell biology in the unique brain microenvironment. This review summarizes the fundamental biology of NK cells and their roles in CNS pathologies, with a focus on their interactions with the CNS niche. We also discuss recent advances, such as immune-engager strategies and adoptive NK cell therapies, aiming to provide insights to guide future therapeutic development for CNS disorders.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteomyelitis: Epidemiology, Classification, Pathophysiology, Clinical Features, Diagnosis, and Management 骨髓炎：流行病学、分类、病理生理学、临床特征、诊断和管理。

IF 14.1

MedComm Pub Date : 2026-09-21 DOI: 10.1002/mco2.70981

Qingqiang Lei, Liangbin Lin, Peidong Pu, Jie Chen, Xianchao Su, Shubao Liu, Yanli Tong, Hui Yu

{"title":"Osteomyelitis: Epidemiology, Classification, Pathophysiology, Clinical Features, Diagnosis, and Management","authors":"Qingqiang Lei, Liangbin Lin, Peidong Pu, Jie Chen, Xianchao Su, Shubao Liu, Yanli Tong, Hui Yu","doi":"10.1002/mco2.70981","DOIUrl":"10.1002/mco2.70981","url":null,"abstract":"Osteomyelitis (OM) is a severe inflammatory bone disease caused by pathogen invasion, representing a major challenge in orthopedic surgery. Staphylococcus aureus (S. aureus) is the predominant causative pathogen across all OM subtypes, and its increasing antibiotic resistance has further complicated clinical management. Despite advances in antibiotic therapy and surgical debridement, treatment failure and disease recurrence remain unacceptably high. Emerging evidence suggests that these poor outcomes are largely attributed to the intricate host–pathogen interplay within the bone microenvironment, yet the underlying immunological mechanisms remain incompletely understood. This review provides a comprehensive overview of the epidemiological characteristics, classification, clinical features, pathophysiology, and current diagnostic and therapeutic strategies for OM, with a particular focus on host immune dysregulation in disease initiation and chronicity, elucidating the mechanisms underlying immunosuppressive niche formation and persistent bone destruction. We further dissect the multifaceted immune evasion strategies employed by S. aureus, including biofilm formation, intracellular persistence, and abscess barrier construction, which collectively drive infection chronicity and progressive bone destruction. By synthesizing recent advances in osteoimmunology, this review identifies critical knowledge gaps and proposes potential targeted immunomodulatory interventions, offering promising avenues to overcome conventional treatment limitations.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brown Adipose Tissue: Molecular Mechanisms of Regulation, Physiological Functions, and Therapeutic Targets 褐色脂肪组织：调控的分子机制、生理功能和治疗靶点。

IF 14.1

MedComm Pub Date : 2026-09-20 DOI: 10.1002/mco2.70976

Xiaoli Deng, Yuanyuan Shen, Ying Sun, Lu Lu, Chongkui Sun

{"title":"Brown Adipose Tissue: Molecular Mechanisms of Regulation, Physiological Functions, and Therapeutic Targets","authors":"Xiaoli Deng, Yuanyuan Shen, Ying Sun, Lu Lu, Chongkui Sun","doi":"10.1002/mco2.70976","DOIUrl":"10.1002/mco2.70976","url":null,"abstract":"Brown adipose tissue (BAT) biology has undergone a profound evolution over the past two decades, expanding from a narrow focus on thermogenic capacity in rodents to the establishment of its pleiotropic roles in human metabolic regulation. While this transition has enabled major progress in defining underlying molecular mechanisms and strengthened the clinical rationale for targeting BAT, it has also exposed unresolved challenges and knowledge gaps. In this review, we synthesize current evidence across the field, integrating findings from molecular, physiological, and translational studies to delineate the hierarchical regulatory networks that govern BAT development and function. We focus on three themes: first, the transcriptional, epigenetic, and posttranscriptional mechanisms that establish and maintain BAT identity; second, the expanding spectrum of BAT's physiological functions beyond thermogenesis, including its crosstalk with other metabolic organs and the immune system; and third, the emerging strategies and persistent obstacles in harnessing BAT's therapeutic potential for obesity, diabetes, and related metabolic disorders. By consolidating these perspectives, we propose an integrative framework for understanding BAT as a central hub in human metabolic regulation while identifying critical knowledge gaps that warrant further investigation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ciliary Ift20 and Wwtr1 Coordinate Transforming Growth Factor-β Receptor II Signaling to Maintain Bone–Fat Balance in Skeletal Homeostasis 纤毛Ift20和Wwtr1协调转化生长因子-β受体II信号，维持骨骼稳态中的骨脂平衡。

IF 14.1

MedComm Pub Date : 2026-09-20 DOI: 10.1002/mco2.70916

Yang Li, Yang Yang, Shuting Yang, Huijuan Chang, Yi-Ping Li, Shuying Yang

{"title":"Ciliary Ift20 and Wwtr1 Coordinate Transforming Growth Factor-β Receptor II Signaling to Maintain Bone–Fat Balance in Skeletal Homeostasis","authors":"Yang Li, Yang Yang, Shuting Yang, Huijuan Chang, Yi-Ping Li, Shuying Yang","doi":"10.1002/mco2.70916","DOIUrl":"10.1002/mco2.70916","url":null,"abstract":"The balance between bone formation and bone marrow adipose tissue accumulation is essential for skeletal integrity, and disruption of this balance contributes to skeletal degeneration, osteoporosis, and metabolic bone loss. However, the molecular mechanisms controlling this balance across skeletal homeostasis and disease remain unclear. Here, transcriptomic analysis of human osteoporotic bone samples revealed significant downregulation of Ift20 and Wwtr1 in osteoblast-lineage cells. Using osteoblast-specific knockout models, we found that loss of both Ift20 and Wwtr1 in the osteoblast lineage caused severe bone loss and excessive bone marrow adipose tissue accumulation, which was further aggravated under ovariectomy and high-fat diet conditions. Mechanistically, Ift20 localized to primary cilia and interacted with transforming growth factor-β receptor II (TβRII), protecting it from c-Cbl-mediated ubiquitination and degradation to sustain TGF-β signaling. Meanwhile, Wwtr1 directly bound the TβRII promoter to promote its transcription. Loss of Ift20 and Wwtr1 converged on TβRII suppression, impairing osteoblast differentiation while enhancing adipogenesis and osteoclastogenesis. These findings reveal a previously unrecognized cilia–transcription–TGF-β regulatory mechanism that governs osteoblast–adipocyte fate decisions and skeletal remodeling. The Ift20–Wwtr1–TβRII axis represents a critical safeguard of bone mass and marrow fat balance and may provide a therapeutic target for osteoporosis and metabolic bone diseases.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular Vesicles: Classification, Biological Functions, Diseases, and Therapeutic Opportunities 细胞外囊泡：分类、生物学功能、疾病和治疗机会。

IF 14.1

MedComm Pub Date : 2026-09-20 DOI: 10.1002/mco2.70896

Sabrina Garbo, Francesco Marocco, Clemens Zwergel, Marco Tripodi, Cecilia Battistelli

{"title":"Extracellular Vesicles: Classification, Biological Functions, Diseases, and Therapeutic Opportunities","authors":"Sabrina Garbo, Francesco Marocco, Clemens Zwergel, Marco Tripodi, Cecilia Battistelli","doi":"10.1002/mco2.70896","DOIUrl":"10.1002/mco2.70896","url":null,"abstract":"Extracellular vesicles (EVs) are lipid bilayer-enclosed particles released by virtually all cell types and act as mediators of intercellular communication in physiology and disease. By transporting diverse bioactive molecules, including proteins, lipids, and nucleic acids, EVs regulate gene expression, modulate immune responses, and support tissue homeostasis. Rapid advances have revealed their heterogeneity, complex biogenesis, and broad functional relevance, as well as their importance as biomarkers and therapeutic delivery systems. The molecular principles governing selective cargo loading remain incompletely understood, particularly for microRNAs: once viewed as passive carriers, EVs are now known to sort miRNAs through regulated mechanisms that do not simply reflect intracellular abundance. In this review, we provide an integrated overview of EV biology, including classification, biogenesis, and roles in health and disease. We focus on mechanisms underlying selective RNA cargo loading, highlighting RNA-binding proteins such as SYNCRIP and PCBP2, sequence features linked to selective export, and epitranscriptomic regulation, including m6A modifications. We also discuss emerging computational and AI-driven approaches to identify RNA–protein interactions and determinants of cargo selection, alongside developments in EV engineering and clinical translation. By bridging mechanistic insights with translational perspectives, this review positions EVs as platforms for precision medicine, biomarker discovery, and RNA-based therapeutics.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myelin Impairment and Regeneration in the Central Nervous System: Molecular Mechanisms, Diseases, and Prospective Therapeutic Targets 髓磷脂损伤和中枢神经系统再生：分子机制、疾病和前瞻性治疗靶点。

IF 14.1

MedComm Pub Date : 2026-09-20 DOI: 10.1002/mco2.71017

Lihong Huang, Peng Cheng, Guangdong Liu, Yang Xiang, Zhen Hong, Weidong Le

{"title":"Myelin Impairment and Regeneration in the Central Nervous System: Molecular Mechanisms, Diseases, and Prospective Therapeutic Targets","authors":"Lihong Huang, Peng Cheng, Guangdong Liu, Yang Xiang, Zhen Hong, Weidong Le","doi":"10.1002/mco2.71017","DOIUrl":"10.1002/mco2.71017","url":null,"abstract":"Myelin plasticity is fundamental to the formation of neural networks and the optimization of neural functions, shaping circuits governing emotion, cognition, sensation, and motor control. Synthesized by oligodendrocytes, myelin undergoes lifelong remodeling that demands high metabolic activity; this renders the myelin-oligodendrocyte unit highly susceptible to metabolic stress, aging, and pathological insults. While demyelination is the core hallmark of various chronic neurological disorders, this review specifically highlights its emerging role in Alzheimer's disease (AD). Myelin impairment is increasingly recognized as an early pathological event in AD, potentially preceding the classic accumulation of amyloid plaques and neurofibrillary tangles. Here, we provide a comprehensive overview of myelin structure and function, evaluating the potential of tracking myelin changes as early diagnostic biomarker for AD. We further synthesize recent evidence regarding myelin pathology across a spectrum of central nervous system disorders including multiple sclerosis, leukodystrophies, cerebral small vessel disease, psychiatric disorders, and traumatic injury, highlighting the underlying pathological mechanisms. Furthermore, we examine emerging therapeutic strategies, ranging from pharmacological interventions to noninvasive stimulation, aimed at restoring oligodendroglial function and promoting remyelination. Finally, we offer a forward-looking perspective on myelin regeneration research, emphasizing its critical potential as a novel therapeutic target for AD and other neurodegenerative conditions.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells 沉睡的巨人：代谢和自噬在休眠多倍体巨型癌细胞的产生和存活。

IF 14.1

MedComm Pub Date : 2026-09-20 DOI: 10.1002/mco2.70873

Silvia Guil-Luna, María Teresa Sánchez-Montero, Alejandra Díaz-Chacón, Antonio Rodríguez-Ariza

{"title":"The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells","authors":"Silvia Guil-Luna, María Teresa Sánchez-Montero, Alejandra Díaz-Chacón, Antonio Rodríguez-Ariza","doi":"10.1002/mco2.70873","DOIUrl":"10.1002/mco2.70873","url":null,"abstract":"A major limitation in preventing cancer relapse is our incomplete understanding of therapy resistance and tumor dormancy, including the role of therapy-induced polyploidy in generating rapidly proliferating progeny that repopulate the tumor. In this context, polyploid giant cancer cells (PGCCs) are a unique subpopulation traditionally considered terminally senescent due to large size, abnormal DNA content, and inability to undergo mitosis. However, compelling evidence shows that PGCCs generate progeny via amitotic mechanisms (neosis), producing highly proliferative, chemo-resistant tumor-initiating cells that drive cancer relapse. Although metabolic adaptations and autophagy support PGCC formation and survival, the mechanisms underlying these processes and their contribution to tumor relapse remain poorly understood. This review explores the complex interplay between autophagy and metabolic adaptations in PGCCs, emphasizing their role in PGCC formation, long-term survival and dormancy, and in the generation of amitotic progeny that drive tumor regrowth and cancer relapse. Mechanistic insights into how autophagy and metabolic plasticity enable PGCCs to withstand stress, maintain energy homeostasis, and escape therapy are highlighted. Additionally, we discuss therapeutic approaches targeting PGCCs by disruption of autophagy and metabolic pathways, evaluating their potential to impair progeny formation, overcome therapy resistance, and prevent cancer recurrence.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tripterine Liposome Exerts Antitumor and Immunomodulatory Effects in Pancreatic Ductal Adenocarcinoma 雷公藤红素脂质体在胰腺导管腺癌中的抗肿瘤和免疫调节作用。

IF 14.1

MedComm Pub Date : 2026-09-20 DOI: 10.1002/mco2.70977

Lirui Tang, Yi Lin, Xueqin Jiang, Xiaohe Tian, Giuseppe Battaglia, Yuquan Wei, Wenshuang Wu, Xuemei He, Xiawei Wei

{"title":"Tripterine Liposome Exerts Antitumor and Immunomodulatory Effects in Pancreatic Ductal Adenocarcinoma","authors":"Lirui Tang, Yi Lin, Xueqin Jiang, Xiaohe Tian, Giuseppe Battaglia, Yuquan Wei, Wenshuang Wu, Xuemei He, Xiawei Wei","doi":"10.1002/mco2.70977","DOIUrl":"10.1002/mco2.70977","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly aggressive phenotype and limited therapeutic options, primarily attributable to diagnostic delays and intrinsic chemotherapy resistance, thereby underscoring the critical need for the development of more effective therapeutic strategies. Tripterine (TP) is a natural compound with potent antitumor activity, but has shown limited clinical use due to its multi-organ toxicity. Here, we overcame this limitation by formulating TP into liposomes (TP-lipo). We evaluated the therapeutic potential of TP-lipo showing that TP-lipo exhibited antitumor activity in vitro (murine Pdx1-Cre/LSL-KrasG12D/+/LSL-Trp53R172H/+ pancreatic cancer cells, KPC cells) and in vivo (PDAC mouse) models. TP-lipo reshaped the tumor immune microenvironment by promoting macrophage polarization toward the M1 phenotype, increasing the proportion of interferon-γ (IFN-γ)-secreting CD8+ T cells. In vitro, TP-lipo promoted IFN-γ and granzyme B production in CD8+ T cells, while TP-lipo-pretreated macrophages enhanced T-cell differentiation into cytotoxic T lymphocytes. Notably, combination therapy with TP-lipo and PD-1 antagonist exerted a synergistic antitumor effect and significantly prolonged median survival in PDAC-bearing mice. TP-lipo showed substantially lower toxicity than the free drug, highlighting its improved safety profile and therapeutic potential. Collectively, these findings suggest TP-lipo, particularly in combination with PD-1 blockade, as a promising therapeutic strategy for PDAC.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Tertiary Lymphoid Structures in Autoimmune Diseases and Cancer. 三级淋巴结构在自身免疫性疾病和癌症中的作用。

IF 14.1

MedComm Pub Date : 2026-09-18 eCollection Date: 2026-09-01 DOI: 10.1002/mco2.70943

Ze Yan, Bin Wen, Ying Hu, Xiaocui Wang, Xuemei Duan, Haonan Li, Shumin Dong, Yufeng Fan, Caihong Wang, Shutong Yang, Huifeng Shang, Yukai Jing

{"title":"Role of Tertiary Lymphoid Structures in Autoimmune Diseases and Cancer.","authors":"Ze Yan, Bin Wen, Ying Hu, Xiaocui Wang, Xuemei Duan, Haonan Li, Shumin Dong, Yufeng Fan, Caihong Wang, Shutong Yang, Huifeng Shang, Yukai Jing","doi":"10.1002/mco2.70943","DOIUrl":"10.1002/mco2.70943","url":null,"abstract":"Tertiary lymphoid structures (TLSs) are ectopic, organized immune aggregates forming in non-lymphoid tissues during chronic inflammation. Resembling secondary lymphoid organs (SLOs) architecturally and functionally, TLSs feature specialized stromal networks and compartmentalized immune cell zones. In autoimmunity, TLSs can perpetuate local immune activation, autoantibody production, and tissue damage, correlating with disease severity and progression. In the tumor microenvironment, TLSs are generally associated with enhanced anti-tumor immunity, improved patient survival, and better responses to immunotherapy, although their functional impact can vary across cancer types. This review systematically examines the structural and functional foundations of TLSs and dissects the mechanisms driving their formation in both autoimmune disorders and cancers. We critically evaluate the clinical correlations of TLSs with disease activity, progression, and patient outcomes. Furthermore, we summarize current methodologies for TLS detection and assess their diagnostic and prognostic utility in disease monitoring. Finally, we discuss emerging therapeutic strategies aimed at modulating TLSs formation or function. By synthesizing current knowledge, this review provides crucial insights into TLSs biology within autoimmunity and cancer, highlighting their potential as novel biomarkers and therapeutic targets, thereby advancing our understanding of disease mechanisms and treatment approaches.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 9","pages":"e70943"},"PeriodicalIF":14.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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