Frontiers in Immunology最新文献

{"title":"Resveratrol and the neuroinflammation axis in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and cerebral ischemia.","authors":"Haoyu Wang, Fei Li, Haifan Wang, Zenan Tian, Hong Fan, Zhibin Shi","doi":"10.3389/fimmu.2026.1758356","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1758356","url":null,"abstract":"<p><p>Resveratrol (RES), a naturally occurring polyphenolic compound found in grapes, berries, and peanuts, has attracted considerable interest because of its antioxidant, anti-inflammatory, and neuroprotective properties. This narrative review examines the current evidence regarding the potential effects of RES on memory-related processes and neuroinflammatory biomarkers in major neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and cerebral ischemia. Relevant literature was identified through searches of major scientific databases, and studies addressing the molecular mechanisms, experimental outcomes, and therapeutic implications of RES in these conditions were evaluated. The available evidence indicates that RES can modulate several biological pathways associated with neurodegeneration, including oxidative stress, inflammatory signaling, mitochondrial dysfunction, and neuronal survival. Experimental studies suggest that RES may influence key molecular mediators such as pro-inflammatory cytokines, nitric oxide (NO) signaling, and matrix metalloproteinases, which are implicated in neuronal damage and blood-brain barrier disruption. In preclinical models of AD and PD, RES has been associated with improvements in cognitive performance, reduction of neuroinflammatory markers, and attenuation of neuronal loss. Similarly, studies in MS and cerebral ischemia models indicate that RES may modulate immune responses, reduce oxidative damage, and limit ischemia-related neuronal injury. However, most of the current evidence derives from <i>in vitro</i> and animal studies, and clinical data remain limited. Moreover, the low bioavailability of RES and variability in dosing regimens represent important challenges for clinical translation. Therefore, although experimental findings support the potential neuroprotective role of RES, further well-designed clinical studies are required to determine its therapeutic relevance and safety in human neurological disorders. This narrative review was developed through a structured search of PubMed, Scopus, and Web of Science for articles published between 2000 and 2024, focusing on mechanistic, preclinical, and clinical investigations of RES in neurological disorders. This review synthesizes current evidence on the molecular and cellular mechanisms underlying the neuroprotective effects of RES, with particular emphasis on its antioxidant, anti-inflammatory, and immunomodulatory activities. By integrating findings from experimental and clinical research, the review highlights the potential of RES to modulate key pathways involved in neurodegeneration and neuroinflammation. Although further well-designed clinical studies are required to clarify its therapeutic efficacy and translational relevance, the available evidence supports continued investigation of RES as a promising candidate for neuroprotective strategies in neurological disorders.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1758356"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining multi-omics analysis methods to identify biomarkers for mitophagy involved in immune checkpoint inhibitors-related myocarditis.","authors":"Jian Yu, Jiangtao Wang, Xinya Liu, Jing Shi, Yang Zhang, Cancan Wang, Li Wu, Yuanming Zhang","doi":"10.3389/fimmu.2026.1691848","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1691848","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are prone to induce cardiovascular adverse reactions during the immunotherapy of cancer patients, among which ICIs-related myocarditis is the most severe. Mitophagy dysregulation is associated with various heart diseases, but its role in ICIs-related myocarditis remains unclear.</p><p><strong>Materials and methods: </strong>Mitophagy key genes in ICIs-related myocarditis were screened based on the single-cell RNA sequencing and bulk RNA sequencing data, and their expression levels and diagnostic value were verified. Meanwhile, the key genes, trajectory analysis and cell interaction were validated at the single-cell level. Finally, the myocardial injury markers, cardiac function indicators, histopathological analysis and mitophagy key genes were verified by constructing a mouse model of ICIs-related myocarditis.</p><p><strong>Results: </strong>A total of 4 mitophagy key genes in ICIs-related myocarditis were identified by combining multiple bioinformatics analysis methods: AW112010, Igfbp7, Tmsb4x, Ost4. The expression levels of mitophagy key genes in the ICIs-related myocarditis group were significantly higher than those in the normal group (<i>P</i> < 0.05 or <i>P</i> < 0.01), and both had high diagnostic value. Trajectory analysis and cell interaction results showed the interaction intensity and relative expression patterns among these 4 key genes. The ICIs-related myocarditis mouse model showed elevated myocardial injury markers (BNP, CK-MB, cTnT) and decreased cardiac function indicators (LVEDV, LVEF, LVIDd, LVIDs) compared to the normal group (<i>P</i> < 0.05 or <i>P</i> < 0.01). The pathological sections revealed obvious inflammation and damage in the myocardium of myocarditis group mice. Additionally, the qRT-PCR results indicated that the expression levels of AW112010, Igfbp7, Tmsb4x and Ost4 were significantly higher than those in the normal group (<i>P</i> < 0.05 or <i>P</i> < 0.01).</p><p><strong>Conclusion: </strong>Mitophagy is involved in the pathogenesis of ICIs-related myocarditis, and AW112010, Igfbp7, Tmsb4x and Ost4 may become potential biomarkers for future clinical practice.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1691848"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral and cytokine responses to a heterologous goatpox vaccine in Mithun (<i>Bos frontalis</i>): a longitudinal field study.","authors":"Gundallahalli Bayyappa Manjunatha Reddy, Vikram Ramesh, Yallappa M Somagond, Plabita Goswami, Selvaraj Ragulraj, Hlawndo Lalzampuia, Suchismitha Pal, Sudeep Nagaraj, Sunil Tadakod, Uzma Jabeen, Shraddha Bijalwan, Muthannan Andavar Ramakrishnan, Baldev Raj Gulati, Patil Shivanagowda Girish","doi":"10.3389/fimmu.2026.1818309","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1818309","url":null,"abstract":"<p><strong>Introduction: </strong>Lumpy Skin Disease (LSD), caused by a Capripoxvirus, has caused severe outbreaks among cattle in India. The disease status and vaccine response of Mithun (<i>Bos frontalis</i>), a semi-domesticated bovine species of major socio-economic importance in Northeast India, remain poorly understood. Because sero-epidemiological findings have indicated LSDV exposure in Mithun, preventive interventions are needed.</p><p><strong>Methods: </strong>We conducted a 12-month longitudinal field study in Nagaland to assess the safety and vaccine-induced immune response of a heterologous goatpox vaccine in seronegative Mithun. Humoral responses were monitored by indirect ELISA and virus neutralization test (VNT), whereas selected systemic cytokine markers (IFN-γ, IL-2, IL-4, and IL-10) were evaluated using serum IFN-γ ELISA and PBMC mRNA transcriptional profiling.</p><p><strong>Results: </strong>Spatial mapping supported continued LSDV activity in Mithun populations. The vaccine was safe, with no adverse clinical reactions or detectable viral shedding in sequential nasal swabs. Seroconversion and cytokine upregulation were evident after vaccination, with antibody responses and cytokine expression peaking at 30 days post-vaccination.</p><p><strong>Discussions: </strong>These findings provide field-based evidence of vaccine-induced humoral and cytokine responses to the heterologous goatpox vaccine in Mithun and generate baseline information for future evaluation of LSD control strategies in this species. Antigen-specific cell-mediated immunity (CMI) was not assessed in this study, as stimulated PBMC recall assays were beyond the scope of the present field study, and should be evaluated in future investigations.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1818309"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Potency assays for use in manufacturing cellular immunotherapies.","authors":"Donald G Phinney, Ryang Hwa Lee, Brian H Johnstone","doi":"10.3389/fimmu.2026.1851463","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1851463","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1851463"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoskeleton-mediated autophagy regulation in neuroimmune contexts: molecular mechanisms and functional perspectives.","authors":"Xingyu Cao, Haolin Zhang, Juan Wang","doi":"10.3389/fimmu.2026.1732775","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1732775","url":null,"abstract":"<p><p>This review systematically summarizes the central roles and molecular mechanisms of the cytoskeletal system-including actin filaments, microtubules (MT), intermediate filaments, and the Septin family-in the regulation of autophagy. The cytoskeleton not only provides a structural framework and facilitates transport for the autophagic process but also acts as a dynamic signaling hub, participating in every stage from autophagosome formation and cargo recognition to targeted trafficking and autophagosome-lysosome fusion. Actin filaments regulate the initiation of autophagy through dynamic assembly, Arp2/3-mediated nucleation, and mechanosensing. Microtubules drive the transport and localization of autophagosomes by relying on \"dynamic instability\" and the \"tubulin code\". Intermediate filaments-such as vimentin-and septins influence autophagy flux by maintaining organelle integrity, forming molecular scaffolds, and establishing diffusion barriers on membranes. This review further discusses the functional implications of this regulatory network in diverse physiological and pathological neuroimmune contexts, including neurodegeneration and aging. Finally, we highlight that targeting the cytoskeleton-autophagy interaction axis may offer novel therapeutic strategies for related diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1732775"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting histamine H4 receptor improves anti-tumoral response in a murine model of breast cancer.","authors":"Ramiro Vázquez, Paula Saibene, Maria Emilia Boix, Mariano Maio, Gabriela Salamone, Luciana Balboa, Mónica Vermeulen","doi":"10.3389/fimmu.2026.1770957","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1770957","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most common malignant tumors in women worldwide. Histamine (HIS) has been associated with either pro-tumor or anti-tumor effects, depending on the receptor evaluated. It exerts its physiological and pharmacological functions through four receptors (H1R-H4R). In breast cancer, it promotes tumor growth by activating H1 and H2 receptors. Furthermore, HIS released into the tumor microenvironment can promote inflammation associated with tumor development and immunosuppression of the immune response. Several years ago, breast cancer was shown to express the H4R, although conflicting data exist; its activation is associated with tumor progression and the development of metastases.</p><p><strong>Methods and results: </strong>In this study, using a murine model of breast cancer with the 4T1 cell line, we investigated in depth the role of H4R in tumor progression. We demonstrated that H4R blockade with the specific antagonist JNJ777120 (JNJ) inhibits tumor cell line proliferation, migratory capacity, and ROS production, while increasing lactate release and rapidly and transiently ERK kinase activation. <i>In vivo</i>, the antitumorigenic effect of JNJ appears to depend on the adaptive immune response, as suggested by the rapid recruitment of CD8⁺ cells, the increased lymphocyte proliferation from JNJ-treated tumors, and the absence of activity in the adaptive immune-deficient Rag1 mice. Moreover, tumor-derived cells showed altered energy metabolism.</p><p><strong>Conclusion: </strong>Taken together, our results demonstrate the dual role of HIS via the H4R in 4T1 cells, modulating not only tumor cell development but also the immune microenvironment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1770957"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA methylation in urological cancers: regulatory logic, biological functions, and clinical relevance.","authors":"Jiahao Peng, Chong Xie, Zhangmin Xie, Feng Tang, Zhiying Wang, Minhao Liu, Li Yu, Chenhao Tang, Ziyang Liu, Zuowei Yuan, Longwei Liao, Xinpan Zou, Xuran Liu, Mingyang Yi, Huangheng Tao, Wei Wei, Tao Liu, Yixiang Liao","doi":"10.3389/fimmu.2026.1790638","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1790638","url":null,"abstract":"<p><p>Urological malignancies, including prostate, bladder, and renal cancers, remain a major clinical challenge because of tumor heterogeneity, disease progression, and therapeutic resistance. In this context, RNA methylation has emerged as an important post-transcriptional regulatory layer in cancer biology. Importantly, the biological consequences of RNA methylation are not dictated by chemical modifications alone, but by coordinated networks of regulatory proteins that install, remove, and interpret these marks, thereby shaping RNA fate and gene expression programs. Among currently studied RNA modifications, N⁶-methyladenosine (m⁶A) provides the most mature mechanistic framework, whereas non-m⁶A regulators remain comparatively less well characterized. In this review, we systematically summarize the regulatory logic underlying RNA methylation-mediated control in urological cancers, with particular emphasis on how distinct classes of regulatory proteins influence RNA stability, translation, metabolism, and other post-transcriptional processes. We further integrate current evidence across multiple RNA methylation types, including m⁶A, 5-methylcytosine (m⁵C), N¹-methyladenosine (m¹A), and N⁷-methylguanosine (m⁷G), while highlighting the relative immaturity of non-m⁶A evidence in these malignancies. We also provide an overview of current m⁶A detection technologies and discuss their methodological strengths, limitations, and appropriate research applications. Beyond mechanistic insights, we discuss the emerging clinical relevance of RNA methylation regulators in urological malignancies, particularly in relation to diagnostic-related evidence, prognostic stratification, immune-related relevance, and treatment-associated adaptation. In addition, we summarize current therapeutic efforts targeting RNA methylation pathways, including small-molecule inhibitors and related translational strategies, while emphasizing their present limitations. Overall, current evidence supports RNA methylation as a biologically important and increasingly translationally relevant framework in urological cancers, but not yet as a clinically mature one.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1790638"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glymphatic-meningeal lymphatic system imbalance: a peripheral-to-central inflammatory bridge in perioperative neurocognitive disorders.","authors":"Hongyou Wang, Xuedong Wang, Nan Liu, Heng Wang, Chunsheng Feng","doi":"10.3389/fimmu.2026.1828809","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1828809","url":null,"abstract":"<p><p>Perioperative neurocognitive disorders (PNDs) are common postoperative complications, particularly in elderly patients. While surgical trauma is known to trigger systemic inflammation, the mechanisms linking peripheral immune activation to perioperative neurocognitive dysfunction remain not fully elucidated. The glymphatic-meningeal lymphatic system is crucial for maintaining homeostasis because it facilitates the exchange of cerebrospinal fluid and interstitial fluid, clears metabolic waste, and eliminates immune mediators. Recent studies have indicated that dysfunction of this clearance axis may contribute to the exacerbation of PNDs. This article explores how perioperative inflammation may influence the glymphatic-meningeal lymphatic system, thereby promoting neuroinflammation. We propose that the interplay between the inflammatory burden and the clearance capacity of the brain is a critical factor in the pathogenesis of PNDs. Through multimodal approaches-integrating advanced imaging techniques, high-dimensional immunogenomic profiling, biofluid biomarkers, and neurophysiological monitoring-we can more comprehensively characterize alterations in glymphatic-meningeal lymphatic function and their interactions with microcirculatory and immune dynamics. Furthermore, we discuss potential therapeutic strategies targeting the glymphatic-meningeal lymphatic system, which could offer clinical insights for the prevention and treatment of PNDs by targeting the underlying mechanisms.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1828809"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duhuo Jisheng Decoction ameliorates experimental intervertebral disc degeneration by modulating immune-inflammatory responses through regulation of macrophage polarization.","authors":"Yongliang Mei, Liquan Wang, Chao Song, Rui Lv, Xianping Xie, Zongchao Liu","doi":"10.3389/fimmu.2026.1774140","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1774140","url":null,"abstract":"<p><strong>Background: </strong>The predominant cause of lower back pain (LBP) is intervertebral disc degeneration (IVDD), which has a substantial financial cost to both individuals and society. In the pathophysiology of IVDD, the immune-inflammatory response is crucial. The number of macrophages in the nucleus pulposus (NP) was positively correlated with the degree of IVDD. The extracellular matrix (ECM) disintegration, pyroptosis, and apoptosis of nucleus pulposus cells (NPCs) have all been demonstrated to have a significant impact on IVDD and are closely linked to immune-inflammatory regulation. Meanwhile, we have shown that Duhuo Jisheng Decoction (DHJSD), which modulates the aforementioned pathways, can significantly alleviate IVDD. It's unclear, nevertheless, if DHJSD can lessen IVDD by regulating macrophage modulation of the immune-inflammatory response.</p><p><strong>Methods: </strong>In this study, we analyzed the relationship between different subtypes of macrophages and IVDD by using single-cell sequencing. Afterwards, bioinformatics techniques were employed to investigate the primary target genes in IVDD. <i>In vitro</i> and <i>in vivo</i> experiments were performed to investigate the mechanism of action of DHJSD in ameliorating IVDD by regulating macrophages.</p><p><strong>Results: </strong>The results of <i>in vivo</i> experiments showed that DHJSD was able to modulate macrophages to regulate the immune-inflammatory response to ameliorate IVDD, and the results of <i>in vitro</i> experiments showed that DHJSD was able to modulate macrophage polarization to regulate the immune-inflammatory response.</p><p><strong>Conclusion: </strong>We discovered that IVDD may be lessened by DHJSD by boosting M2 macrophage polarization and suppressing M1 macrophage polarization. IVDD responded better to DHJSD treatment in the intermediate and advanced stages of the disease.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1774140"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast cell release of TNF-α indirectly contributes to recalling B cells in the colorectal cancer milieu through the CCL20/CCR6 axis.","authors":"Viviana Valeri, Francesca Mion, Silvia Tonon, Eleonora Martinis, Elena Jachetti, Roberta Sulsenti, Eleonora Capezzali, Serena Battista, Alessandro Mangogna, Laura Mariuzzi, Marco Fontanot, Beatrice Belmonte, Valeria Cancila, Claudio Tripodo, Marta Mozzon, Alessandro Uzzau, Barbara Frossi, Carlo Pucillo","doi":"10.3389/fimmu.2026.1725902","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1725902","url":null,"abstract":"<p><strong>Introduction: </strong>In colorectal cancer (CRC), mast cells (MCs) modulate tumor and immune cell interactions, influencing patient prognosis, though their role remains not fully elucidated. Our group previously uncovered that in the intestine MCs provide support for the effector functions of B cells, both in physiology and inflammation.</p><p><strong>Methods: </strong>In this work we investigated the relationship between the activation of MCs in CRC and recruitment and accumulation of B cells in the tumor environment.</p><p><strong>Results: </strong>We observed infiltration of both B cells and MCs in the tumor tissue and uncovered accumulation of CCR6⁺ B cells in tumor lymph nodes (LNs), both in the mouse model and in human patients. Enhanced expression of the CCL20 chemokine, the ligand of CCR6, was observed in cancer tissue compared to the normal condition, along with an increased CCL20 gradient in mouse tumor-draining LNs. We proved that TNF-α released by activated-MCs was required to sustain CCL20 production from cancer cells <i>in vitro</i>.</p><p><strong>Discussion: </strong>The accumulation of CCR6⁺ B cells in CRC context may then rely on the crosstalk between MCs and CRC cells. Our findings suggest that B cell immunosurveillance may be indirectly promoted through the clinical modulation of TNF-α secretion at the early stages of colorectal tumorigenesis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1725902"},"PeriodicalIF":5.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}