Immunology letters最新文献

{"title":"Neutrophil extracellular traps and reactive oxygen species: Predictors of prognosis in bladder cancer","authors":"Zahra Mansourabadi ,&nbsp;Mohammad-Ali Assarehzadegan ,&nbsp;Fereshteh Mehdipour ,&nbsp;Ali Ariafar ,&nbsp;Zahra Faghih ,&nbsp;Elahe Safari","doi":"10.1016/j.imlet.2025.106991","DOIUrl":"10.1016/j.imlet.2025.106991","url":null,"abstract":"<div><div>Neutrophils, the most abundant leukocytes in circulation, have become the subject of intensive research due to growing evidence of their role as modulators of cancer with both anti- and pro-tumorigenic effects. However, their prognostic function related to the release of neutrophil extracellular traps (NETs) and production of reactive oxygen species (ROS) has not yet been elucidated in the context of bladder cancer (BC). This study aimed to evaluate the ability of circulating neutrophils from BC patients to undergo NETosis and produce ROS—both spontaneously and following activation with phorbol 12-myristate 13-acetate (PMA)—using flow cytometry and immunofluorescence techniques. Their relevance to clinicopathological characteristics was also evaluated. Our results showed that PMA-treated neutrophils had increased early NETosis in patients with stage II (<em>P</em> = 0.048) and T2 (<em>P</em> = 0.014) compared to those with stage III and T3, respectively. These cells also showed a significant increase in ROS production in patients with T2 compared to those with T3 (<em>P</em> = 0.026) and T4 (<em>P</em> = 0.014), as well as in patients with stage II compared to stage IV (<em>P</em> = 0.048). Additionally, spontaneous ROS production was higher in patients without lymphovascular invasion than in those with invasion (<em>P</em> = 0.013). The increased activity of neutrophils observed in earlier stages (stage II and T2) suggests a potential protective mechanism in the early phases of cancer progression. It also highlights NETosis and ROS production by neutrophils as possible biomarkers for assessing disease progression. These findings provide insights into the complex interactions of neutrophils within the tumor microenvironment and lay the groundwork for further investigations into targeted therapies, potentially improving prognostic evaluations and treatment outcomes for patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106991"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nobiletin ameliorates monosodium urate-induced gouty arthritis in mice by enhancing AMPK/mTOR-mediated autophagy to inhibit NF-κB/NLRP3 inflammasome activation","authors":"Zhiyong Liu ,&nbsp;Aichun Chu ,&nbsp;Zhiqian Bai ,&nbsp;Chao Yang","doi":"10.1016/j.imlet.2025.106982","DOIUrl":"10.1016/j.imlet.2025.106982","url":null,"abstract":"<div><h3>Background</h3><div>Gouty arthritis (GA) is a common rheumatic disease caused by the release of monosodium urate crystal (MSU) deposits into joint space. Nobiletin is a polymethoxylated flavonoid isolated from citrus fruits and has many beneficial activities. This study aimed to elucidate the therapeutic efficacy of nobiletin in GA and to reveal its potential mechanisms.</div></div><div><h3>Methods</h3><div>Phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 macrophages were primed with lipopolysaccharide (LPS) and then stimulated with MSU crystals in the presence or absence of nobiletin. Cell viability as well as the levels of proinflammatory cytokines, pathway-related proteins, NLRP3 inflammasomes, and autophagy-related proteins were evaluated. MSU was used to induce GA in mice. Hematoxylin-eosin staining was conducted to assess histological morphology changes. Immunofluorescence staining was performed to measure LC3 expression in THP-1 cells and ankle joint tissues.</div></div><div><h3>Results</h3><div>For <em>in vitro</em> analysis, nobiletin reduced LPS and MSU-induced cell viability inhibition. Additionally, nobiletin inhibited inflammation and NF-κB/NLRP3 pathway in THP-1 cells. Moreover, nobiletin inhibited the activation of NLRP3 inflammasome by promoting AMPK/mTOR-mediated autophagy. For <em>in vivo</em> analysis, nobiletin attenuated MSU-induced GA in mice. Additionally, nobiletin suppressed inflammation and NF-κB/NLRP3 pathway and promoted tissue autophagy in GA mice.</div></div><div><h3>Conclusion</h3><div>Nobiletin prevents MSU-induced GA in mice by inhibiting NF-κB/NLRP3 inflammasome activation through AMPK/mTOR-mediated autophagy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 106982"},"PeriodicalIF":3.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP7 - A novel target for controlling periodontal inflammation through modulation of macrophage polarization","authors":"Yan Wang ,&nbsp;Hailin Mu ,&nbsp;Baochen Yang ,&nbsp;Chang Yang,&nbsp;Wei Dong,&nbsp;Jiawei Wang","doi":"10.1016/j.imlet.2025.106981","DOIUrl":"10.1016/j.imlet.2025.106981","url":null,"abstract":"<div><div>Disruption of local microbial irritation and host immune response can result in inflammation and tissue destruction in periodontitis. Studies on the modulation of macrophage polarization could help attenuate immune responses in periodontal tissues. To investigate the effect of ubiquitin-specific protease-7 (USP7) and its inhibitor P5091 on the polarization of macrophages in periodontitis, gene expression in periodontitis tissues and normal control were analyzed via single-cell RNA sequencing data and mice model experimental periodontitis. RAW264.7 cells were induced to M1 polarization with LPS + IFN-γ and M2 polarization with IL-4. USP7 was knocked down using lentivirus, and the effect of USP7 inhibitor P5091 on macrophage polarization was comparatively analyzed. The expression of Usp7 and polarization markers were detected by qRT-PCR. Western blot was used to examine the polarization markers and pathway-associated proteins. Results indicated that USP7 expression was elevated in tissues affected by periodontitis. Periodontitis macrophages and M1 polarized macrophages had higher USP7 expression. Knockdown of USP7 revealed an inhibition of both M1 and M2 macrophage polarization. Inhibition of USP7 with P5091 resulted in the decreased expression of M1 polarization markers and phosphorylation of P65, but the increased expression of M2 polarization markers and phosphorylation of STAT6. In conclusion, USP7 is involved in regulating macrophage polarization in periodontitis and its inhibitor P5091 may contribute to the prevention of periodontitis.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106981"},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of efgartigimod in patients with neurological autoimmune diseases","authors":"Jin Qin ,&nbsp;Wei Li,&nbsp;Lipin Yuan,&nbsp;Huiqin Liu,&nbsp;Rui Pang,&nbsp;Jiewen Zhang","doi":"10.1016/j.imlet.2025.106983","DOIUrl":"10.1016/j.imlet.2025.106983","url":null,"abstract":"<div><h3>Objective</h3><div>Myasthenia gravis (MG) is an autoimmune disease characterized by disrupted neuromuscular synaptic transmission. Efgartigimod, a human Fc receptor antagonist, has been approved for patients with MG. Its potential use for other IgG-mediated neurological autoimmune diseases is unclear. This study aimed to retrospectively evaluate the efficacy and safety of efgartigimod in patients with neurological autoimmune diseases.</div></div><div><h3>Methods</h3><div>This retrospective study investigated patients with neurological autoimmune diseases who were treated with efgartigimod in the Henan Provincial People's Hospital. The efficacy of the medication was analyzed using the quality-of-life improvement score and the IgG level pre- and post-efgartigimod treatment. The safety of the medication was assessed by considering adverse events and blood parameters. The blood parameters, including routine blood parameters, coagulation, liver, kidney, and immune function.</div></div><div><h3>Results</h3><div>Seventeen patients received efgartigimod in the Henan Provincial People's Hospital from September 1, 2023, to January 31, 2024. In MG patients, myasthenia gravis activities of daily living (MG-ADL) reduced after efgartigimod treatment for 4 weeks compared with baseline (<em>P</em> &lt; 0.05). Autoimmune encephalitis (AE) is a group of inflammatory disease with antibodies against neuronal synaptic and cell surface antigens. Similarly, patients with AE had a statistically significant reduction in modified Rankin scale (mRS) after efgartigimod treatment for 4 weeks compared with baseline (<em>P</em> &lt; 0.05). Guillain Barre syndrome (GBS) is an immune-mediated disease of the peripheral nerves and nerve roots. However, the inflammatory neuropathy cause and treatment (INCAT) scale score didn't statistically differ in GBS patients before and after efgartigimod treatment (<em>P</em> &gt; 0.05). The IgG levels significantly reduced after the first infusion and gradually decreased after multiple infusions (<em>P</em> &lt; 0.05). Most subjects did not have increased IgG serum levels before treatment. IgA, IgM, and complement levels didn't differ significantly with efgartigimod treatment (<em>P</em> &gt; 0.05). There were no changes in blood parameters during the treatment (<em>P</em> &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Efgartigimod was effective and safe in neurological IgG-mediated autoimmune diseases, even in patients without increased IgG serum levels.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106983"},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic and cerebrospinal fluid immune mediators coordinate a dichotomic microenvironment in parturients with acute or convalescent phases of COVID-19","authors":"Lizandra Moura Paravidine Sasaki ,&nbsp;Maria Eduarda Canellas-de-Castro ,&nbsp;Geraldo Magela Fernandes ,&nbsp;Felipe Motta ,&nbsp;David Alves Araújo Júnior ,&nbsp;Heidi Luise Schulte ,&nbsp;Gabriela Profírio Jardim-Santos ,&nbsp;Ângelo Pereira Silva ,&nbsp;Aleida Oliveira Carvalho ,&nbsp;Yacara Ribeiro Pereira ,&nbsp;Clara Correia Siracusa ,&nbsp;Isadora Pastrana Rabelo ,&nbsp;Agenor de Castro Moreira Santos Junior ,&nbsp;Caroline de Oliveira Alves ,&nbsp;Lucas Lauand ,&nbsp;Rodrigo de Resende Nery ,&nbsp;Dayde Lane Mendonça-Silva ,&nbsp;Rosana Tristão ,&nbsp;José Alfredo Lacerda Jesus ,&nbsp;Karina Nascimento Costa ,&nbsp;Licia Maria Henrique Mota","doi":"10.1016/j.imlet.2025.106979","DOIUrl":"10.1016/j.imlet.2025.106979","url":null,"abstract":"<div><div>The present study intended to characterize the profile of soluble immune mediators in serum samples and in the cerebrospinal fluid (CSF) microenvironment from parturients with acute and convalescent COVID-19 as compared to healthy controls (HC), during the circulation of B.1.1.28 and B.1.1.33 SARS-CoV-2 strains, which were identified during the initial spread of COVID-19 in Brazil. Data demonstrated increased levels of immune mediators in serum at acute infection with a clear waning during convalescent COVID-19. Conversely, a progressive increase of immune mediators was observed in CSF from acute infection towards convalescent COVID-19. Immune mediator signatures and integrative correlation circuits further confirmed these findings and supported the existence of dichotomic microenvironments in the serum and CSF compartments. While a waning of correlations involving pro-inflammatory cytokines with increased connectivity of regulatory cytokines was observed in serum samples from acute towards convalescent COVID-19, an increasing frequency of correlations mediated by pro-inflammatory cytokines with decreased connectivity of regulatory cytokine was the hallmark of CSF. Correlations analysis identified a set of molecules associated with the dichotomic crosstalk between serum and CSF compartments, including chemokines (CXCL8, CCL5, CXCL10) and regulatory cytokines (IL-4 and IL-9). These immune biomarkers may represent potential targets for therapeutic strategies in parturients with COVID-19. Together, these findings demonstrated the existence of a divergent landscape of soluble immune mediators in serum and CSF, emphasizing the relevance of understanding the systemic and compartmentalized immune response elicited by SARS-CoV-2 infection during pregnancy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 106979"},"PeriodicalIF":3.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-21 promotes plasmablast differentiation independently of proliferation in vitro","authors":"Marcus James Robinson,&nbsp;David Mathew Tarlinton","doi":"10.1016/j.imlet.2025.106980","DOIUrl":"10.1016/j.imlet.2025.106980","url":null,"abstract":"<div><div>Antibodies of the IgE and IgG1 isotypes are relevant for type 2 immunity. <em>In vivo</em>, the production of both is elevated by IL-4, but differentially affected by IL-21, with IgE suppressed and IgG1 production enhanced by IL-21. However, whether the cytokines drive these outcomes primarily by impacting antibody-secreting, proliferating plasmablasts (PB), or their germinal center B cell precursors, is challenging to unravel. <em>In vitro</em> analyses using Nojima cultures, wherein naïve B cells are activated on fibroblasts co-expressing CD40L and BAFF, allows for evaluation of this problem. Here, we explore how IL-4 and IL-21 alone and in combination affect Nojima-cultured B cell proliferation and fate, asking what is unique or redundant about exposure to each. In secondary culture, as expected, IL-21 amplified replicative expansion. IL-21 also selectively promoted the differentiation of IgG1⁺ B cells into PB. The effect was countermanded by synchronous exposure to IL-4, suggesting competing signaling pathways are triggered by the two cytokines independently. Secondary culture with IL-4 alone promoted IgE⁺ B cell genesis without increasing replicative expansion. Combined exposure to IL-21 and IL-4 led to increased IgE class-switching and proliferative expansion, suggesting that once B cells are switched to IgE, IL-21 can promote IgE+ B cell proliferation. Thus, in culture IL-21 operates to promote proliferation and also drives differentiation of IgG1+ B cells into PB whereas IL-4 has an ongoing role in IgE B cell genesis. The balance of IL-4 and IL-21 thus impacts the fate of <em>in vitro-</em>generated germinal center B cells and highlights how the notable IgE-suppressing effects of IL-21 <em>in vivo</em> likely precede the class-switch step, after which IL-21 may amplify IgE production by virtue of its pro-proliferative effects.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106980"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382368","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":"Maternal immunoglobulins differentially bind a diverse bacterial community in human colostrum and the stool of breastfed neonates","authors":"Karina Corona-Cervantes ,&nbsp;Erick Sánchez-Salguero ,&nbsp;Paola Berenice Zárate-Segura ,&nbsp;Aparna Krishnakumar ,&nbsp;Alberto Piña-Escobedo ,&nbsp;Martín Noé Rangel-Calvillo ,&nbsp;Tito Ramírez-Lozada ,&nbsp;Gustavo Acosta-Altamirano ,&nbsp;Noemí del Socorro Lázaro-Pérez ,&nbsp;Mónica Sierra-Martínez ,&nbsp;Leopoldo Santos-Argumedo ,&nbsp;Jaime García-Mena","doi":"10.1016/j.imlet.2025.106978","DOIUrl":"10.1016/j.imlet.2025.106978","url":null,"abstract":"<div><div>In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strains is an interesting topic of research where maternal immunoglobulins appear to be important. This proof-of-concept study explored the binding pattern of IgA1, IgA2, IgM, and IgG classes to a commensal bacterial in human colostrum and the stool of breastfed neonates. We used flow cytometry coupled with 16S rRNA gene sequencing in human colostrum and neonatal feces samples to characterize this Ig-microbiota association. We observed that in human colostrum samples, IgA2 and IgM bind alfa and beta Proteobacteria, which can potentially stimulate neonatal immune system development in the gut. Other immunoglobulins like IgG predominantly bind facultative anaerobes belonging to the Firmicutes phylum, reported as part of human milk microbiota and pioneer colonizers of the neonatal gut. Maternal immunoglobulins also bind a wide diversity of bacteria in the neonatal stool. For instance, IgA2 and IgM bound more members of the phylum Bacteroidetes in comparison to IgG, these Bacteroidetes and some firmicutes have been reported as late colonizers of the neonatal gut, and their presence is important due to their ability to produce important short chain fatty acids like propionate and butyrate. Our results support the current view that microbial and immunoglobulin transference is crucial for developing the neonate's immune system and individual gut microbiota.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106978"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382375","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":"In virto priming of the STING signaling pathway enhances the maturation and activation of dendritic cells induced by hepatitis B vaccine","authors":"Chaomin Ren ,&nbsp;Xufeng Cui ,&nbsp;Huixin Wang ,&nbsp;Cong Jin ,&nbsp;Linying Gao ,&nbsp;Yandi Li ,&nbsp;Weigang Wang ,&nbsp;Tian Yao ,&nbsp;Demei Zhang ,&nbsp;Yongliang Feng ,&nbsp;Keke Wang ,&nbsp;Suping Wang","doi":"10.1016/j.imlet.2025.106977","DOIUrl":"10.1016/j.imlet.2025.106977","url":null,"abstract":"<div><div>This study investigates the role of the STING signaling pathway in enhancing dendritic cells (DCs) maturation and activation in response to the hepatitis B vaccine. By analyzing the GSE52894 dataset, we compared differentially expressed genes between mature dendritic cells (mDCs) and immature dendritic cells (iDCs). In vitro, iDCs were treated with the STING agonist 2′3′-cGAMP, either alone or in combination with lipopolysaccharide (LPS) or the hepatitis B vaccine, to assess the expression of costimulatory molecules and key signaling molecules in the STING pathway, including STING, pNF-κBp65, and pIRF3. The results indicated that mDCs expressed significantly higher levels of STING mRNA compared to iDCs (<em>P</em> &lt; 0.01). Treatment with 2′3′-cGAMP increased STING expression and activated downstream signaling molecules pNF-κBp65 and pIRF3. Co-treatment with 2′3′-cGAMP and LPS upregulated costimulatory molecules (CD80, CD86, HLA-DR, CD11c) more effectively than LPS alone (<em>P</em> &lt; 0.05). Co-treatment with 2′3′-cGAMP and the hepatitis B vaccine resulted in significantly higher expression of costimulatory molecules compared to vaccine-only treatment. Furthermore, co-treatment with 2′3′-cGAMP and the hepatitis B vaccine enhanced STING, pNF-κBp65, and pIRF3 expression relative to vaccine alone. Mixed lymphocyte reaction assays demonstrated that the 2′3′-cGAMP and hepatitis B vaccine co-treatment group had a significantly stronger effect on the proliferation of CD4⁺<em>T</em> cells compared to the vaccine-only treatment group. In conclusion, 2′3′-cGAMP enhances DCs maturation and promotes CD4⁺<em>T</em> cells proliferation in response to the hepatitis B vaccine by activating the STING/IRF3 and STING/NF-κB pathways, highlighting its potential as an adjuvant to improve vaccine efficacy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"272 ","pages":"Article 106977"},"PeriodicalIF":3.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of microplastics on the immune system: How much should we worry?","authors":"Claudia Vanetti ,&nbsp;Martina Broggiato ,&nbsp;Stefania Pezzana ,&nbsp;Mario Clerici ,&nbsp;Claudio Fenizia","doi":"10.1016/j.imlet.2025.106976","DOIUrl":"10.1016/j.imlet.2025.106976","url":null,"abstract":"<div><div>Plastics are everywhere. It is widely recognized that they represent a global problem, the extent of which is yet to be defined. Humans are broadly exposed to plastics, whose effects and consequences are poorly characterized so far. The main route of exposure is via alimentary and respiratory intake. Plastics pollutions may come from both: water and food contamination itself, and their packaging. The smaller sizes (<em>i.e.</em> microplastics &lt;150 µm - MPs) are considered to be the most pervasive of living organisms and, therefore, potentially the most harmful. As humans occupy one of the apex positions of the food chain, we are exposed to bioaccumulation and biomagnification effects of MPs. In fact, MPs are commonly found in human stools and blood. However, there are no data available yet on their ability to accumulate and to produce detrimental consequences on biological systems. Even though the effects of plastics pollution are poorly studied in mammals, including humans, they appear to have inflammatory effects, which is rather concerning as many etiologies of disease are based on a pro-inflammatory status.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"272 ","pages":"Article 106976"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122865","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":"Th1 adjuvant ARNAX, in combination with radiation therapy, enhances tumor regression in mouse tumor-implant models","authors":"Aya Miyazaki ,&nbsp;Sumito Yoshida ,&nbsp;Yohei Takeda ,&nbsp;Utano Tomaru ,&nbsp;Misako Matsumoto ,&nbsp;Tsukasa Seya","doi":"10.1016/j.imlet.2024.106947","DOIUrl":"10.1016/j.imlet.2024.106947","url":null,"abstract":"<div><div>Radiation therapy (RT) rarely induces tumor regression at untreated metastatic sites, the so-called abscopal effect. A syngeneic tumor (EG7) transplanted into a Th1-dominant mouse strain (C57BL/6) regressed significantly on the treated side and less on the contralateral side after RT. Additional subcutaneous administration of ARNAX, a non-inflammatory adjuvant, further accelerated tumor regression on the untreated side. This suggests that ARNAX after RT significantly enhances the tumor regression effect on the irrelevant tumor.</div><div>Based on this setting, we next observed similar tumor shrinkage after RT and ARNAX by transplanting syngeneic breast cancer tumors (4T1) into a Th2-dominant mouse strain (BALB/c). The results were as follows: 1. ARNAX enhanced RT-mediated tumor shrinkage comparable to polyI:C; 2. In the Th2 mouse strain, little tumor regression occurred on the untreated side compared to tumor regression on the treated side after RT alone; 3. RT+ARNAX treatment caused additive regression on the treated side and induced slight tumor regression on the untreated side; 4. PD-L1 antibody + RT combination therapy caused tumor regression and further induced additive regression with ARNAX; 5. The combination of RT and ARNAX reduced the number and volume of lung metastases compared to RT alone. However, tumor regression was not always accompanied by a significant prolongation of survival in the mice receiving our regimen and protocol (one 10Gy radiation and a single ARNAX treatment). In conclusion, RT therapy promoted abscopal tumor regression in both Th2 and Th1 models with the addition of the non-inflammatory adjuvant ARNAX.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"271 ","pages":"Article 106947"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739251","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}