Immunobiology最新文献

{"title":"Complement at the crossroads of inflammation and metabolism: implications for diabetes and metabolic functions","authors":"Vaishnavi Dandavate,&nbsp;Anna M. Blom,&nbsp;Ben C. King","doi":"10.1016/j.imbio.2025.153113","DOIUrl":"10.1016/j.imbio.2025.153113","url":null,"abstract":"<div><div>Diabetes is a growing global problem, with hundreds of millions of people living with the disease worldwide. Diabetes can be divided into two major subtypes, autoimmune type 1 diabetes (T1D), and type 2 diabetes (T2D), which has stronger causal links in obesity, lifestyle, and age. Although immunity and inflammation are clearly defined in T1D, it is also understood that inflammation has a role in metabolic dysregulation in T2D, inducing insulin resistance as well as affecting β-cell function, survival, and therefore insulin secretion. Cytokines and other inflammatory mediators can affect function of cells important for metabolism, most studied in adipose tissue, muscle, and pancreatic islets. Similarly, evidence shows that complement can also have positive roles in metabolic homeostasis in adipose tissue and pancreatic islets. This review will give an introduction to this field, with focus on established and emerging roles of the complement system, an arm of humoral innate immunity that has been found to have roles in metabolic homeostasis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153113"},"PeriodicalIF":2.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085992","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":"Research progress of animal models of antigen-induced autoimmune diseases","authors":"Haixiang Zhang ,&nbsp;Jingying Sun ,&nbsp;Chunyan Guo ,&nbsp;Cuixiang Xu ,&nbsp;Jun Hu","doi":"10.1016/j.imbio.2025.153111","DOIUrl":"10.1016/j.imbio.2025.153111","url":null,"abstract":"<div><div>Autoimmune diseases (AID) are chronic debilitating diseases characterized by excessive or prolonged autoimmune responses, which lead to the destruction of normal tissue structures and consequent clinical symptoms. AID poses a significant threat to human health, and its pathogenic mechanism remains poorly understood. Etiological studies suggest that the onset of AID primarily caused by the combined influence of environmental and genetic factors. The development of stable and effective animal models is a crucial approach and method for studying the pathogenesis of AID and for accurate prevention and treatment. This paper presents a review of the classification of immune antigens, heterophilic antigen epitopes, and the role of autoantigens in the construction of AID animal models, focusing particularly on the establishment of antigen-induced AID animal models, aiming to provide theoretical references for subsequent research on AID.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153111"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926157","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":"CD1-MR1 2024 unconventional immune surveillance: Uniting a rapidly growing field.","authors":"Hui-Fern Koay","doi":"10.1016/j.imbio.2025.153110","DOIUrl":"https://doi.org/10.1016/j.imbio.2025.153110","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":" ","pages":"153110"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006052","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":"Stability testing of HPCs and MNCs from apheresis products","authors":"Jinxia Ma,&nbsp;Lipei Shao,&nbsp;Tatyana Fuksenko,&nbsp;Hui Liu,&nbsp;Chunjie Jiang,&nbsp;Yihua Cai,&nbsp;Yong Soo Kim,&nbsp;Kathryn Martin,&nbsp;Larry Moses,&nbsp;Nan Zhang,&nbsp;Anh Dinh,&nbsp;Robert P. Somerville,&nbsp;David F. Stroncek,&nbsp;Ping Jin","doi":"10.1016/j.imbio.2025.153112","DOIUrl":"10.1016/j.imbio.2025.153112","url":null,"abstract":"<div><h3>Background</h3><div>Hematopoietic progenitor cells (HPCs) and mononuclear cells (MNCs) are critical components of cell-based therapies, including bone marrow transplantation and regenerative treatments. Evaluation of the characteristics of these products during collection, storage, and transport is essential for maintaining cell viability and functionality. In this study, we evaluated the functional and molecular stability of samples collected for the evaluation of fresh HPC and MNC products. The samples stored at 4 °C for up to 4 days and were evaluated using white blood cell (WBC) counts, flow cytometry, and bulk RNA sequencing (RNA-seq) across five time points.</div></div><div><h3>Methods</h3><div>HPC samples from seven products (June–December 2022) and MNC samples from six products (October 2022–August 2023) were analyzed on days 0 through 4 after collection. WBC counts were measured, and viability was assessed using 7-AAD staining and flow cytometry. HPC samples were stained with antibodies against CD34, CD3, CD19, CD56, CD14, CD16, CD15, and CD45, while MNC samples were stained with antibodies directed to CD3, CD4, CD8, CD19, CD56, CD14, CD16, CD15, and CD45. Total RNA was isolated from each sample and subjected to bulk RNA-seq to assess transcriptomic changes during storage.</div></div><div><h3>Results</h3><div>While WBC counts varied between products, no significant differences were observed across time points within individual products. Flow cytometry markers remained relatively stable over time in both HPC and MNC samples, although greater variability was observed in HPCs. A modest decrease in lymphocyte percentages was noted at later time points, primarily driven by a reduction in CD3+ cells; however, these changes were not statistically significant. Cell viability declined significantly over time within individual products and showed inter-product variability. RNA-seq analysis revealed stable gene expression profiles in MNC samples across all time points. In contrast, HPC samples exhibited notable transcriptomic changes as early as day 1 of storage at 4 °C, indicating greater molecular instability.</div></div><div><h3>Conclusion</h3><div>WBC counts and flow cytometry markers remain stable for up to 3 days in samples collected from fresh HPC and MNC products when stored at 4 °C, although cell viability progressively declines. However, RNA-seq data reveal early transcriptomic changes in HPC samples, suggesting that immediate evaluation of these samples is critical to preserve their molecular integrity and functionality. These findings support the feasibility of delayed phenotypic analysis but emphasize the need for prompt molecular assays in HPC-based applications.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153112"},"PeriodicalIF":2.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005236","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":"Increase CD24+CD27+ B cells within pleural effusions derived from lung adenocarcinoma presents enhanced potential for clinical utility","authors":"Yueming Liang ,&nbsp;Danqi Sun ,&nbsp;Qizhi Xu ,&nbsp;Xiaofan Mao ,&nbsp;Minjing Li ,&nbsp;XingLin Gao ,&nbsp;Sifei Yu","doi":"10.1016/j.imbio.2025.153109","DOIUrl":"10.1016/j.imbio.2025.153109","url":null,"abstract":"<div><h3>Background</h3><div>The increasing interest in the roles of B cells, particularly regulatory B cells, within the tumor microenvironment has become prominent, though their immunological characteristics in malignant pleural effusions (PE) remain poorly elucidated.</div></div><div><h3>Methods</h3><div>Flow cytometry was performed in 143 pleural effusion and peripheral blood samples from patients in order to analyze the proportions of<!--> <!-->PB-derived B and T cells, and to assess surface markers and cytokines, such as IFN-γ and IL-10. Moreover, we compared clinical role of CD24⁺CD27⁺ <!-->B cell populations.</div></div><div><h3>Results</h3><div>B cell populations were significantly higher in PE from lung adenocarcinoma (LUAD)<!--> <!-->than tuberculosis (TB). Compared to PB from patients, the proportion of CD24⁺CD27⁺ B cells was markedly elevated in LUAD-PE and exhibited reduced levels of CD38, CD5, CD71,<!--> <!-->PD-1, and PD-L1, as well as an upregulation of IL-10 and CD39. PD-1 and PD-L1 were<!--> <!-->largely found to be upregulated within the CD27⁺CD38⁺ B cell subset despite declining proportions overall. <em>Re</em>-interpretations illustrated significant relationships<!--> <!-->between CD24⁺CD27⁺ B cells and clinical measurements.</div></div><div><h3>Conclusions</h3><div>This study highlights the heterogenic<!--> <!-->phenotypes and functions of various B cell subsets in LUAD-PE, with specific attention to CD24⁺CD27⁺ B cells as potential diagnostic markers and the need for further studies investigating their immunoregulatory functions to unveil new immunotherapeutic strategies in lung cancer.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153109"},"PeriodicalIF":2.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904225","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":"UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice","authors":"Dalei Sun ,&nbsp;Shu Ouyang ,&nbsp;Xiaoxuan Xu ,&nbsp;Jingjing Yan ,&nbsp;Heqian Wang ,&nbsp;Chenkai Lan ,&nbsp;Wubin Ouyang ,&nbsp;Liangjun Zhong ,&nbsp;Jun Lin","doi":"10.1016/j.imbio.2025.153108","DOIUrl":"10.1016/j.imbio.2025.153108","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate the therapeutic and ameliorative effects of the Myeloid Cell Leukemia 1 protein (MCL-1) inhibitor UMI-77 on experimental murine periodontitis via mitophagy activation, with a focus on comparing administration routes (local/intraperitoneal) and doses (high/low/combined).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A ligature-induced periodontitis model was established in 54 male C57BL/6 J mice, randomized into 9 groups (&lt;em&gt;n&lt;/em&gt; = 6 per group): normal control (Group Aa), periodontitis model (Group Ab), positive control (Group Ac, local minocycline), local PBS control (Group Ad), intraperitoneal PBS control (Group Ae), local high-dose UMI-77 (Group Ba, 2 mg/kg), local low-dose UMI-77 (Group Bb, 1 mg/kg), intraperitoneal UMI-77 (Group Ca, 2 mg/kg), and combined intraperitoneal UMI-77 + local minocycline (Group Cb, 2 mg/kg + standard minocycline regimen). Outcomes included periodontal bleeding on probing (BOP), alveolar bone resorption via micro-CT, histopathological analysis (HE/methylene blue staining), MCL-1 expression (Western blot), autolysosome detection (transmission electron microscopy, TEM), and systemic organ safety (HE staining).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;All UMI-77 treatment groups exhibited significant amelioration of periodontal inflammation and bone resorption compared to the model group (Ab, &lt;em&gt;p&lt;/em&gt; &lt; 0.0001). Local high-dose UMI-77 (Group Ba) demonstrated the most potent efficacy, reducing BOP by 76 % (0.67 ± 0.5 vs. Ab: 2.8 ± 0.4, &lt;em&gt;p&lt;/em&gt; &lt; 0.001) and cementoenamel junction–alveolar bone crest distance by 48.7 % (0.20 ± 0.04 mm vs. Ab: 0.41 ± 0.05 mm, &lt;em&gt;p&lt;/em&gt; &lt; 0.0001), outperforming the positive control (Group Ac, BOP: 2.17 ± 0.4, &lt;em&gt;p&lt;/em&gt; &lt; 0.001). Histological analysis showed reduced inflammatory cell infiltration and organized periodontal fibers in Group Ba. Western blot confirmed downregulation of MCL-1 expression to near-normal levels in Group Ba, while TEM detected autolysosomes in both Group Ba and Group Ca, indicating mitophagy activation. Systemic safety assessments revealed only mild grade 1 cardiac septal thickening in Group Ba and transient splenic lymphocyte elevation in Group Ca, with no severe organ toxicity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;UMI-77 exerts significant therapeutic and ameliorative effects against periodontitis in mice, with local high-dose administration (Group Ba) demonstrating optimal efficacy. Intraperitoneal UMI-77 combined with local minocycline (Group Cb) achieved comparable outcomes to high-dose local UMI-77, highlighting potential combinatorial strategies. These findings establish UMI-77 as a promising agent for periodontitis treatment via MCL-1-targeted mitophagy activation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical significance&lt;/h3&gt;&lt;div&gt;UMI-77, especially with local high-dose administration, offers a new, potentially effective and safe approach for periodontitis treatment, holding great promise for clinical translation.&lt;/div&gt;&lt;/","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153108"},"PeriodicalIF":2.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890277","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":"Proportional and functional anomalies of CD38+ NK Cells:A new mechanism for impaired anti-tumour immunity in multiple myeloma?","authors":"Huixian Chen ,&nbsp;Kehua Fang ,&nbsp;Jinbao Zong ,&nbsp;Xiaotian Chang","doi":"10.1016/j.imbio.2025.153107","DOIUrl":"10.1016/j.imbio.2025.153107","url":null,"abstract":"<div><h3>Background</h3><div>The abnormal quantity and dysfunction of immune cells in patients with multiple myeloma impede anti-tumour immunity and prompt the occurrence and development of disease. It has been reported that CD38⁺ NK cells are involved in immune regulation.</div></div><div><h3>Methods</h3><div>Peripheral blood (PB) samples were collected from healthy volunteers (HV) and newly diagnosed multiple myeloma (NDMM) patients. The proportions of CD38⁺ NK cells and CD38⁺CD16⁺ NK cells were measured. Moreover, CD38⁺ NK cells separated from PB were co-cultured with RPMI-8226 assess their impact on myeloma cell apoptosis and proliferation. Similar co-culture experiments were also initiated with naive CD4⁺ T cells from HV to ascertain the influence of CD38⁺ NK cells on regulatory T cells (Tregs) differentiation.</div></div><div><h3>Results</h3><div>The percentages of CD38⁺ NK and CD38⁺CD16⁺ NK cells in the PB of NDMM patients were markedly decrease than that in HV. The apoptosis rate of RPMI-8226 was slightly increased following co-culture with CD38⁺ NK cells from NDMM samples, as opposed to those from HV samples. CD38⁺ NK cells from NDMM or HV had similar inhibitory effect on MM cell proliferation. Furthermore, CD38⁺ NK cells from NDMM fostered CD4⁺ T cell differentiation to Tregs more than those from HV.</div></div><div><h3>Conclusion</h3><div>In MM, the proportion and function of CD38⁺ NK cells undergo changes, which may be related to the formation of the immunosuppressive microenvironment.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153107"},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865011","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":"Prior appendectomy attenuates the immune protective efficacy of BCG vaccination against Mycobacterium tuberculosis infection","authors":"Huirong Huang ,&nbsp;Wei Xu ,&nbsp;Sidong Xiong","doi":"10.1016/j.imbio.2025.153106","DOIUrl":"10.1016/j.imbio.2025.153106","url":null,"abstract":"<div><div>Cecal appendix is a unique niche for commensal bacteria, and has been considered the primary site for immunoglobulin A production. Yet its immune function in anti-infection immunity has not been fully understood. In order to elucidate whether cecal patch (CeP), the murine version of appendix, would influence the immune response induced by <em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) and the vaccine effect of Bacillus Calmette-Guérin (BCG), BALB/c mice at 4 weeks of age received appendectomy or sham operation and recovered for 2 weeks before intranasal infection with 2 × 10⁷ CFU <em>Mycobacterium tuberculosis</em> H37Ra. Appendectomy of mice led to a reduction in lung macrophage numbers 7 days post infection (p. i.), and aggravated lung immunohistopathology 4 weeks p. i.. Appendectomized mice vaccinated with 5 × 10⁶ CFU BCG exhibited attenuated BCG-specific serum IgG, reduced lung/splenic IFN-γ⁺ T response, and weakened T proliferation and cytotoxicity, and eventually worsened lung pathology compared to sham operated mice. Mechanistically, we found that appendectomized mice at a young age (4 weeks) had an attenuated maturation of mesenteric lymph node (MLN) conventional dendritic cells (cDCs), which accounted for the impaired systemic IFN-γ⁺ T response and cytotoxicity against <em>M. tb</em>. Our data suggest that intact appendix maintain intestinal DC maturation and systemic Th1 induction against <em>M. tb</em> and has an assistant role in increasing immune efficiency of BCG vaccine.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153106"},"PeriodicalIF":2.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852223","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":"Serological assessment of rubella immunity in Iranian children post 2019 elimination: A pilot study","authors":"Tasnim Jamalvandi ,&nbsp;Akram Sadat Ahmadi ,&nbsp;Somayeh Shatizadeh Malekshahi ,&nbsp;Maryam Tatari ,&nbsp;Azadeh Shadab ,&nbsp;Vahid Salimi ,&nbsp;Nazanin-Zahra Shafiei-Jandaghi ,&nbsp;Talat Mokhtari-Azad","doi":"10.1016/j.imbio.2025.153105","DOIUrl":"10.1016/j.imbio.2025.153105","url":null,"abstract":"<div><h3>Background and aim</h3><div>The elimination of rubella in Iran, achieved in 2019, represents a significant public health success. A limited number of studies have investigated rubella IgG seropositivity levels in Iran across different populations over the last two decades. This study evaluated rubella vaccination coverage and immunity status among Iranian children born between 2016 and 2021, before and during the COVID-19 pandemic.</div></div><div><h3>Methods</h3><div>Using ELISA, 722 serum samples from children negative for measles and rubella IgM antibodies were analyzed for rubella-specific IgG. Samples were divided into two groups: Group A (born 2016–2018, pre-pandemic) and Group B (born 2019–2021, during the pandemic). Vaccination status was obtained from parental reports.</div></div><div><h3>Results</h3><div>Overall rubella IgG seropositivity was 75.3 %, with Group B showing significantly higher immunity (82.4 %) than Group A (68.6 %) (<em>p</em> &lt; 0.001). Parental reports indicated MMR vaccination coverage of 95.7 % overall, with Group B coverage (98.9 %) significantly exceeding Group A (92.7 %) (p &lt; 0.001). No significant gender differences were observed. Regional vaccination coverage varied, but rubella IgG positivity was consistent across provinces.</div></div><div><h3>Conclusions</h3><div>Despite maintaining high MMR vaccination coverage, the overall rubella immunity level in Iranian children in this pilot study remained below the WHO's recommended herd immunity threshold, posing a potential risk for rubella re-emergence. This finding underscored the ongoing surveillance and targeted immunization efforts to sustain rubella elimination in Iran.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153105"},"PeriodicalIF":2.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827635","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":"Kasumi-1 exosome plays a major T-cell immune evasion role in TP53-type acute leukemia","authors":"Yunyun Du ,&nbsp;Zhenfeng Fan ,&nbsp;Lijiao Li ,&nbsp;Yong Xue ,&nbsp;Shixiang Zhao","doi":"10.1016/j.imbio.2025.153102","DOIUrl":"10.1016/j.imbio.2025.153102","url":null,"abstract":"<div><h3>Background</h3><div>The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.</div></div><div><h3>Methods</h3><div>Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.</div></div><div><h3>Results</h3><div>In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8⁺ T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.</div></div><div><h3>Conclusion</h3><div>Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8⁺ T cell expression and increased Treg expression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153102"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656501","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}