Immunobiology最新文献

{"title":"MicroRNA-5011-5p attenuates LPS-induced inflammatory damage in periodontal ligament cells by targeting KLF6: an in vitro study","authors":"Yuanjie Shi,&nbsp;Yinyao Ma,&nbsp;Xiao Liu","doi":"10.1016/j.imbio.2026.153207","DOIUrl":"10.1016/j.imbio.2026.153207","url":null,"abstract":"<div><div>Periodontitis is a long-term inflammatory condition that leads to the breakdown of the structures supporting the teeth and loss of bone. MicroRNAs are important regulators in controlling inflammation and maintaining tissue balance. This study explores the function of miR-5011-5p in periodontal ligament cells (PDLCs) under lipopolysaccharide (LPS)-induced inflammatory stress. It investigates its regulatory relationship with KLF6, a transcription factor implicated in inflammation and apoptosis. In periodontal ligament cells stimulated with LPS, the expression of miR-5011-5p decreased, accompanied by a notable increase in KLF6 and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Functional assays revealed that overexpression of miR-5011-5p suppressed cytokine production, promoted cell viability, and reduced apoptosis. Conversely, reintroduction of KLF6 reversed these protective effects. Experiments using dual-luciferase reporter assays verified that KLF6 is a direct target regulated by miR-5011-5p. Additionally, Western blot results demonstrated that miR-5011-5p increased the levels of the anti-apoptotic protein Bcl-2 while decreasing the pro-apoptotic protein Bax, effects that were reversed when KLF6 was overexpressed. These findings suggest that miR-5011-5p mitigates LPS-induced periodontal inflammation and apoptosis by suppressing KLF6 expression. The miR-5011-5p and KLF6 interaction pathway could serve as a novel molecular target for developing therapies to treat periodontitis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153207"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ST2-mediated ERK/JNK/P38/NF-κB signaling: a target of Biminkang mixture in minimal persistent inflammation of allergic rhinitis","authors":"Meng Sun,&nbsp;Xiaojing Zhang,&nbsp;Wei Meng,&nbsp;Lifeng Zhang,&nbsp;Xiangjing Chen,&nbsp;Xin Zhang,&nbsp;Yunhong Ning,&nbsp;Renzhong Wang","doi":"10.1016/j.imbio.2026.153210","DOIUrl":"10.1016/j.imbio.2026.153210","url":null,"abstract":"<div><h3>Background</h3><div>Minimal persistent inflammation (MPI) significantly contributes to the recurrence of allergic rhinitis (AR). Although the therapeutic efficacy of Biminkang mixture (BMK) in AR treatment is well-documented, the precise mechanisms underlying its modulation of MPI remain unclear.</div></div><div><h3>Methods</h3><div>An MPI mouse model and an interleukin-33 (IL-33)-induced T-helper 2 (Th2) cell model were established. The effects of BMK on nasal mucosa remodeling and inflammation in MPI mice were evaluated using hematoxylin &amp; eosin staining and ELISA. Th2 cell viability was measured using a CCK-8 assay. Western blotting and qRT-PCR were performed to evaluate the effects of BMK on the ST2/ERK/JNK/P38/NF-κB signaling cascade.</div></div><div><h3>Results</h3><div>Administration of BMK notably mitigated nasal mucosa remodeling and inflammation in MPI mice and markedly inhibited IL-33-induced Th2 cell viability. Moreover, BMK inhibited the activation of the ST2/ERK/JNK/P38/NF-κB signaling cascade, and the inhibit effect of BMK on the ERK/JNK/P38/NF-κB pathway was further enhanced by silencing ST2.</div></div><div><h3>Conclusions</h3><div>These findings suggest that BMK effectively alleviates MPI by targeting the ST2-mediated ERK/JNK/P38/NF-κB pathway, thereby inhibiting nasal mucosa remodeling, inflammation, and Th2 cell viability.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153210"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monomethyl-auristatin E-based anti-CD137 (4-1BB) antibody drug conjugates are not suitable tools to deplete activated T lymphocytes","authors":"Gabriel Gomis,&nbsp;Saioa Arrieta-Aranzueque,&nbsp;Claudia Herrero,&nbsp;Arantza Azpilikueta,&nbsp;Paula Molero-Glez,&nbsp;Raquel Cuesta,&nbsp;Luca Streitlein,&nbsp;Christian Kleist,&nbsp;Walter Mier,&nbsp;María J. Garrido,&nbsp;Federica Rochira,&nbsp;Antonio Pineda-Lucena,&nbsp;Pedro Berraondo,&nbsp;Ignacio Melero","doi":"10.1016/j.imbio.2026.153205","DOIUrl":"10.1016/j.imbio.2026.153205","url":null,"abstract":"<div><div>CD137 (4-1BB) is a surface marker selectively expressed on activated T cells, whose induction depends on antigen recognition, and is readily internalized upon ligand recognition. These factors make it an attractive target for antibody-drug conjugates (ADCs). Selective elimination of CD137⁺ T cells could represent a therapeutic strategy in autoimmune diseases, allograft rejection, and graft-versus-host disease. In this study, we aimed to generate and evaluate anti-human and anti-mouse CD137 ADCs for their ability to kill CD137-expressing cells. ADCs were produced from monoclonal antibodies by stochastic conjugation of active esters to lysine residues. The generated ADCs bound effectively and specifically to CD137 on stable Jurkat and HEK-293T transfectants, and were efficiently internalized. In transfectants expressing high CD137 surface levels, selective cytotoxicity was observed upon incubation with ADCs. Human and mouse T-cell blasts were generated in vitro with anti-CD3/anti-CD28-coated beads to evaluate killing using flow cytometry. However, despite testing different drug-to-antibody ratios (DARs), the ADCs failed to kill activated T-cell blasts of either human or murine origin, and they did not ameliorate experimental graft-versus-host disease in mice. These findings demonstrate that although anti-CD137 ADCs can be successfully engineered to bind and internalize into CD137⁺ cells, the evaluated approaches did not achieve therapeutic elimination of pathogenic T lymphocytes.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153205"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the diagnostic value of ANCA in autoimmune diseases of patients with refractory rhinosinusitis","authors":"Qian Li,&nbsp;Hang Li,&nbsp;Haiyuan Zhao","doi":"10.1016/j.imbio.2026.153222","DOIUrl":"10.1016/j.imbio.2026.153222","url":null,"abstract":"<div><div>Anti-neutrophil cytoplasmic antibody (ANCA) is an important serological marker for autoimmune diseases, particularly ANCA-associated vasculitis (AAV). AAV frequently presents with refractory rhinosinusitis as an initial manifestation, yet ANCA testing in patients with rhinosinusitis continues to face challenges, including inconsistent subtype classification, variable detection performance, and difficulties in early identification, leading to misdiagnosis and delayed treatment. This narrative review focuses on the diagnostic value of ANCA in AAV-related rhinosinusitis, encompassing granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). We summarize the research progress on ANCA detection and its association with clinical, imaging, and pathological features, aiming to provide a theoretical reference for early clinical diagnosis, individualized intervention, and improved patient prognosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153222"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational identification of natural inhibitors of human neutrophil elastase as potential therapeutics for chronic obstructive pulmonary disease","authors":"SK Redwan Zaman,&nbsp;Mst. Shahnaj Parvin,&nbsp;Masuma Akter,&nbsp;Kazi Muhtasim Fuad,&nbsp;Shibli Rubatul Islam,&nbsp;Munna Mondol,&nbsp;Md. Ekramul Islam","doi":"10.1016/j.imbio.2026.153209","DOIUrl":"10.1016/j.imbio.2026.153209","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disorder in which human neutrophil elastase (HNE, encoded by ELANE) plays a central role in extracellular matrix degradation and airway remodeling. Despite its therapeutic relevance, no clinically approved HNE inhibitors are currently available for COPD treatment. In this study, an integrated computational strategy combining virtual screening, molecular docking, network pharmacology, and functional enrichment analysis was employed to identify potential natural inhibitors of HNE.</div><div>A library of 8747 phytochemicals from 64 medicinal plants was screened using Lipinski's rule of five, yielding 1326 drug-like candidates. Molecular docking against HNE, with Bay-85-8501 as a reference inhibitor, identified 33 compounds exhibiting binding affinities stronger than −8 kcal/mol. ADMET profiling further prioritized four lead compounds (CID-13783711, CID-344133, CID-442449449, and CID-10365741) with favorable pharmacokinetic and toxicity profiles.</div><div>Protein–protein interaction network (PPIN) analysis revealed 24 overlapping COPD-associated targets, with ELANE and CXCL8 emerging as key hub proteins interconnected with CAMP, MPO, TLR4, and MMP9, highlighting a neutrophil-driven inflammatory module. Gene Ontology enrichment indicated significant involvement in serine-type endopeptidase activity, acute inflammatory response, and bacterial stimulus pathways, while KEGG analysis identified enrichment in NF-κB, Toll-like receptor, NOD-like receptor, and IL-17 signaling pathways.</div><div>Overall, this study provides a comprehensive computational framework for identifying natural HNE inhibitors and elucidates their potential mechanistic roles within COPD-associated inflammatory networks. The identified lead compounds warrant further validation through molecular dynamics simulations and experimental studies to support their development as therapeutic candidates.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153209"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rFgl2-treated CD32b+M2 macrophages effectively inhibits cardiac transplant rejection in mice","authors":"Wenbin Ji,&nbsp;Baotong Zhang,&nbsp;Jiansheng Zhang,&nbsp;Guoshan Chen,&nbsp;Weiwei Wang,&nbsp;Feng Qi","doi":"10.1016/j.imbio.2026.153197","DOIUrl":"10.1016/j.imbio.2026.153197","url":null,"abstract":"<div><h3>Background</h3><div>The search for additional therapies against acute rejection is warranted. Alternatively activated macrophages (M2 macrophages) have immunomodulatory functions, and enhancement of their immunomodulatory capacity is a feasible complementary therapy. Fcγ receptor II b (FcγRIIb, CD32b), which is highly expressed by M2 macrophages, and its important ligand, fibrinogen-like protein 2 (Fgl2), are immunosuppressive molecules, and it is necessary to explore the potential of both to enhance the immunomodulatory capacity of M2 macrophages.</div></div><div><h3>Methods</h3><div>In vitro, CD32b⁺M2 macrophages obtained by magnetic bead sorting were treated with recombinant Fgl2 (rFgl2) to explore their immunomodulatory capacity under simulated inflammatory (lipopolysaccharide+interferon γ) stimuli and the possible mechanisms using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and western blotting (WB), and they were co-cultured with CD4⁺T cells to explore their modulation of the polarization of regulatory T cells (Tregs).</div><div>In vivo, rFgl2-treated CD32b⁺M2 macrophages were used to treat abdominal heart transplantation model mice, and systemic inflammation, changes in systemic proportions of macrophages, CD4⁺, CD8⁺T cells, and Tregs, and infiltration in grafts were examined using ELISA, hematoxylin-eosin staining, immunohistochemistry, and flow cytometry.</div></div><div><h3>Results</h3><div>In vitro CD32b⁺M2 macrophages treated with rFgl2 further expressed IL-10 and TGF-β1 and had increased levels of phosphorylation of SHP2 and STAT3, which effectively increased the proportion of Tregs after co-culture with CD4⁺T cells. In vivo rFgl2-treated CD32b⁺M2 macrophages increased the proportion of M2 macrophages and Tregs, improved systemic inflammation, attenuated graft injury, reduced inflammatory cell infiltration, and prolonged graft survival.</div></div><div><h3>Conclusions</h3><div>rFgl2 promotes the differentiation of Tregs by activating SHP2 and thus promoting STAT3 activation, which in turn promotes the secretion of the inflammation-suppressing cytokine IL-10 as well as TGF-β1. rFgl2-treated CD32b⁺M2 macrophages alleviate the acute rejection of cardiac transplants in mice by promoting differentiation of M2 macrophages as well as Tregs, which can be used as a complementary treatment to reduce the adverse effects of immunosuppression and prolong the survival time of allogeneic transplants.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153197"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The T cell receptor associated transmembrane adaptor 1 regulates the threshold for activation of naïve human CD4+ T cells","authors":"Xiaolei Wang,&nbsp;Yuxia Zhang,&nbsp;Esther Bandala-Sanchez,&nbsp;Marco J. Herold,&nbsp;Gaetano Naselli,&nbsp;Yifan Zhan,&nbsp;Nicholas D. Huntington,&nbsp;Leonard C. Harrison","doi":"10.1016/j.imbio.2026.153219","DOIUrl":"10.1016/j.imbio.2026.153219","url":null,"abstract":"<div><div>T cell fate is partly determined by T cell receptor (TCR) affinity for its cognate peptide ligand. During thymic selection, CD4⁺ T cells with higher affinity for self-antigens are more likely to be deleted or become FOXP3⁺ natural T regulatory (nTreg) cells. However, downstream transmembrane adaptor proteins such as the T cell receptor associated transmembrane adaptor 1 (TRAT1) also modulate T cell activation. Here we show that TRAT1 decreases the activation threshold of human naïve CD4⁺ T cells and mediates TCR activation leading to transient FOXP3 expression via FOXO3A. Individuals at high risk for autoimmune type 1 diabetes (T1D) had increased proportions of CD4⁺ T cells with elevated TRAT1 expression in their naïve CD4⁺ T cell compartment. Naïve CD4⁺ T cells transduced with an insulin-specific TCR-TRAT1 construct exhibited enhanced proliferation, even in the absence of exogenously added insulin peptide, and showed heightened sensitivity to low doses of insulin peptide. These findings reveal an additional layer of T cell reactivity regulation independent of TCR affinity, which may underlie homeostatic and pathogenic functions of human T cells.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153219"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes of systemic immune cells subtypes in colorectal carcinoma patients","authors":"Khin Aye Thin,&nbsp;Andrew Cross,&nbsp;Phonthep Angsuwatcharakon,&nbsp;Apiwat Mutirangura,&nbsp;Charoenchai Puttipanyalears,&nbsp;Thomas Pike,&nbsp;Robert Jones,&nbsp;Paul Skaife,&nbsp;Steven W. Edwards","doi":"10.1016/j.imbio.2026.153220","DOIUrl":"10.1016/j.imbio.2026.153220","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) can induce stresses on the immune system that can affect both the numbers and function of immune cells. Changes in immune cell functions can also occur during ageing and these may affect both the ability to fight infections and to protect against cancers. As the incidence of CRC is age-related, the aim of this work was to identify changes in immune cell subtypes that are specific to CRC and not merely due to age-related changes.</div></div><div><h3>Methods</h3><div>Whole blood samples from 49 CRC patients about to undergo surgery and 22 healthy controls were collected. Samples were analysed by immunophenotyping, detection of HLA-DR on T-lymphocytes and monocytes, and senescent-like T-lymphocytes.</div></div><div><h3>Results</h3><div>CD4 staining intensity of monocytes was significantly increased in CRC patients and showed a positive correlation with their HLA-DR staining intensity. In most CRC patients, the numbers of helper T-lymphocytes were lower with the progression of the disease, while cytotoxic T-lymphocytes were higher (an opposite pattern to the immunophenotypes of the healthy ageing cohort). NK^bright cells were higher while NK^dim cells were lower in patients with large tumours. An increase in the T-lymphocytes to B-lymphocytes ratio correlated with the metastatic status.</div></div><div><h3>Conclusions</h3><div>Complex changes in the immune phenotypes in CRC, distinct from those that occur during ageing were observed, that imply development of an immuno-suppressive phenotype that may aid tumour evasion of immunity.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153220"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WD-3 improves anti-PD-L1 therapy by remodeling the tumor immune microenvironment through gut microbiota","authors":"Yifei Shi,&nbsp;Qing Xue,&nbsp;Yun Yuan,&nbsp;Yuzhen Li,&nbsp;Xiaodan Zhu,&nbsp;Dong Niu,&nbsp;Chunhui Jin","doi":"10.1016/j.imbio.2026.153215","DOIUrl":"10.1016/j.imbio.2026.153215","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) ranks as the fifth most prevalent malignancy globally. Emerging evidence implicates gut microbiome as a key modulator of anti-tumor immunity and immunotherapy response. Traditional Chinese Medicine (TCM) presents a promising yet underexplored avenue for microbiome modulation.</div></div><div><h3>Methods</h3><div>16S rDNA sequencing of fecal samples was used to detect changes of gut microbiota in advanced GC patients. GC models were established in huPBMC-NOG-dKO mice after fecal microbiota transplantation (FMT) to investigate the potential synergy between Number 3 Prescription (WD-3) and anti-PD-L1 monoclonal antibody (mAb) in treatment of non-responders.</div></div><div><h3>Results</h3><div>In this study, WD-3 combined with αPD-L1 showed additive benefit after the FMT of non-responders in the humanized mouse model model. WD-3 combination therapy correlated with reduced proportion of Treg cell infiltration in tumors. WD-3 combination was also associated with increased species richness and improved gut microbiota community structure compared to αPD-L1 alone, with increased relative abundances of <em>Enterobacteriaceae</em> and <em>Lachnospiraceae</em>.</div></div><div><h3>Conclusion</h3><div>Our data provide correlative evidence that WD-3 supplementation combined with αPD-L1 treatment may attenuate GC progress in the FMT mouse model, indicating association with the modulation of gut microbiota. These findings aim to provide treatment strategies for the clinical treatment of advanced GC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153215"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic stress promotes colorectal cancer progression by inducing M2 macrophage polarization and activating the CCL2-CCR2 axis","authors":"Mengyun Wang,&nbsp;Jiayu Pang,&nbsp;Wenbin Wang,&nbsp;Qian Xu,&nbsp;Yanjie Lu,&nbsp;Yanzhen Zuo,&nbsp;YuHong Li","doi":"10.1016/j.imbio.2026.153211","DOIUrl":"10.1016/j.imbio.2026.153211","url":null,"abstract":"<div><div>Chronic stress is associated with poor prognosis in colorectal cancer (CRC), but the underlying immune mechanisms remain poorly defined. This study investigates how β-adrenergic signaling, a key component of the stress response, modulates the tumor microenvironment. We demonstrate that stressed CRC patients have elevated serum CCL2, and high tumoral expression of CCL2 and its receptor CCR2 predicts poor survival. Single-cell analysis reveals that within the tumor microenvironment of colorectal cancer, macrophages constitute the primary subset of immune cells responsible for CCL2 secretion. Mechanistically, we demonstrate that stimulating macrophages with isoproterenol, a well-established in vitro method to mimic chronic stress signaling, induces their polarization toward an M2-like phenotype and significantly increases CCL2 secretion. Functionally, conditioned media from these “stressed” macrophages enhanced CRC cell proliferation and invasion in a CCR2-dependent manner, an effect abrogated by pharmacological CCR2 blockade. Collectively, our findings pinpoint the CCL2-CCR2 pathway as the central mediator of a ‘stress-macrophage-tumor’ axis, validating it as a key therapeutic target to intercept CRC progression driven by a chronic stress state elicited by β-adrenergic activation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153211"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}