Immunologic Research最新文献

{"title":"The spatial architecture of tumor immunity: Emerging predictive biomarkers across cancer.","authors":"Xiaoying Li, Ruizhen Li, Huanhuan Wang, Pei Zhang, Dan Cao, Fan Zhang","doi":"10.1007/s12026-026-09844-5","DOIUrl":"10.1007/s12026-026-09844-5","url":null,"abstract":"<p><p>Tumor immunity is shaped not only by the cellular composition of the tumor microenvironment (TME), but also by its spatial architecture. Increasing evidence shows that immune function cannot be inferred from cell abundance alone, because the positioning and coordination of immune and stromal cells determine whether local immunity is activated, excluded, or suppressed. Advances in multiplex imaging, spatial proteomics, spatial transcriptomics, and AI-assisted tissue analysis now enable high-resolution mapping of these spatial states across clinically relevant scales. These approaches reveal that tumors are organized as recurrent microarchitectures that can function either as immune engines or as suppressive brakes. Immune-supportive structures, including mature tertiary lymphoid structures, dendritic cell-centered immune triads, high endothelial venule-associated recruitment corridors, and effector-tumor interfaces, promote antigen presentation, lymphocyte recruitment, and cytotoxic engagement. In contrast, exclusionary and suppressive architectures, such as CAF-mediated stromal barriers, SPP1 + macrophage-CAF niches, stalled T-cell zones, Treg-enriched suppressive niches, and NLRP3 + macrophage-rich regions, restrict infiltration and sustain immune dysfunction. Across cancer types, such spatial readouts are emerging as robust biomarkers. In this Review, we summarize recent progress in spatial tumor immunology and propose a conceptual framework for interpreting tumor immunity from composition to cellular neighborhoods. We further discuss how these spatial architectures shape tumor heterogeneity, therapeutic response, and resistance, and how they may be translated into actionable biomarkers for patient stratification, treatment monitoring, and next-generation precision immunotherapy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955797","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":"Clinical Course and Treatment Outcomes of Vulvar Condylomas in Immunocompromised Women: A Retrospective Cohort Study.","authors":"Fernanda Villar Fonseca, Camilly Eduarda Kmita, Carlos Afonso Maestri, Isabela Ceschin Maestri, Renato Nisihara","doi":"10.1007/s12026-026-09843-6","DOIUrl":"10.1007/s12026-026-09843-6","url":null,"abstract":"<p><p>Human papillomavirus (HPV) infection is highly prevalent worldwide and is associated with a broad spectrum of anogenital diseases, including vulvar condylomas and malignancies. Immunosuppression plays a key role in HPV persistence, recurrence, and progression; however, data on the clinical course of vulvar condylomas in immunocompromised women remain limited. This retrospective cohort study evaluated clinical progression, treatment response, recurrence, and neoplastic outcomes in women diagnosed with vulvar condyloma between January 2008 and January 2021 at a tertiary referral center in Brazil. Immunosuppressed patients, including women living with HIV, those receiving immunosuppressive therapy for autoimmune diseases, and patients undergoing chemotherapy, were compared with an age-matched immunocompetent group. Among 294 women included, 41 (13.9%) were immunosuppressed. Lesion extent was significantly greater in immunosuppressed patients, although lesion number did not differ between groups. Clinical remission after first-line treatment was significantly lower among immunosuppressed women (21.9%vs55.0%; p < 0.0001; OR = 4.5) with a higher need for multiple treatment sessions. Similarly, the complete remission rate at the end of follow-up was higher for the immunocompetent patients (75.9% vs. 48.8%; p < 0.0001; OR = 3.3). Immunosuppressed women had a 2.3-fold increased risk of recurrence and a higher risk of progression to vulvar intraepithelial neoplasia (OR = 6.7) and invasive disease (OR = 8.5). In the HIV patients, recurrence was not associated with CD4T-lymphocyte count or HIV viral load. These findings indicate that immunosuppressed women with vulvar condylomas experience more extensive disease, poorer treatment response, higher recurrence rates, and an increased risk of neoplastic progression, highlighting the importance of closer surveillance and individualized management in this high-risk population.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955812","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":"Trained immunity induction by β-glucan under distinct immune training schemes in a mouse model.","authors":"Miriam Angulo, Carlos Angulo","doi":"10.1007/s12026-026-09840-9","DOIUrl":"10.1007/s12026-026-09840-9","url":null,"abstract":"<p><p>Although trained immunity has been explored in various experimental models, the effects of oral β-glucan administration in mice and in vivo comparisons of different training intervals remain unexplored. First, this study evaluated the ability of β-glucan from Debaryomyces hansenii CBS 8339 (βG-Dh) to induce trained immunity in mice through oral administration at different doses. BALB/c mice received oral βG-Dh (0.5, 1, or 2 mg), oral zymosan (1 mg), or intraperitoneal zymosan (1 mg; positive control), followed by ex vivo stimulation of splenocytes with LPS. Low (0.5 mg) and medium (1 mg) doses of βG-Dh significantly enhanced cell viability, nitric oxide production, and myeloperoxidase activity. βG-Dh also increased glucose consumption and lactate production, indicating glycolytic changes associated with trained immunity. In addition, different training schemes were assessed by varying the time intervals (7, 11, and 15 days) between stimulus and challenge. Only the long-time protocol was associated with higher cell survival, increased myeloperoxidase activity, and metabolic changes consistent with a trained immunity phenotype. Overall, these results highlight the critical role of both dosage and stimulation interval in shaping trained immunity outcomes and provide new insights for optimizing β-glucan-based strategies to modulate innate immune memory.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929851","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":"Maternal systemic lupus erythematosus and the risk of congenital cardiovascular abnormalities in offspring: a systematic review and meta-analysis.","authors":"Kuaifa Fang, Lifu Tan, Lianyue Wu","doi":"10.1007/s12026-026-09839-2","DOIUrl":"10.1007/s12026-026-09839-2","url":null,"abstract":"<p><p>Maternal systemic lupus erythematosus (SLE) has been associated with adverse fetal outcomes; however, the risk of structural cardiovascular malformations and congenital heart block (CHB) remains incompletely characterized. This systematic review and meta-analysis quantified the incidence of these two distinct outcomes in offspring of mothers with SLE and explored possible correlates. Electronic databases were searched through January 2026. The pooled prevalence was estimated using random-effects models with the Freeman-Tukey double arcsine transformation. Pooled odds ratios (ORs) were calculated for comparative analyses. Exploratory meta-regression and prespecified subgroup analyses were performed to explore sources of heterogeneity. Multivariable-adjusted estimates were synthesized when available. Fifty-three studies comprising 33,694 SLE-associated pregnancies were included. The pooled incidence was 3.29% (95% CI: 2.48-4.21%) for structural cardiovascular malformations (41 studies, 32,133 pregnancies) and 1.29% (95% CI: 0.82-1.88%) for CHB (45 studies, 28,117 pregnancies). In exploratory study-level meta-regression, active disease rate was positively associated with structural malformations (P = 0.024). For CHB, subgroup analysis showed higher prevalence in studies in which CHB cases occurred in anti-SSA/Ro-positive mothers (2.64%) than in studies not reporting antibody status (0.63%; P-interaction < 0.001). Compared with healthy controls, offspring of mothers with SLE had a significantly increased risk of structural malformations (OR 3.52, 95% CI: 2.13-5.81; P < 0.001), which persisted in a pooled analysis of five multivariable-adjusted studies (OR 1.70, 95% CI: 1.22-2.36; P = 0.002), although confounder adjustment was heterogeneous and incomplete across studies. For CHB, the comparative risk estimate was elevated but highly imprecise and statistically unstable. Maternal SLE is associated with an increased risk of structural cardiovascular malformations in offspring, whereas evidence for CHB is less robust and limited by rare-event instability and antibody-status heterogeneity. The independent contribution of SLE itself remains uncertain because of incomplete adjustment for antibody status, disease activity, medication exposure, and surveillance intensity. Future prospective studies with rigorous confounder adjustment are warranted to clarify the independent effect of SLE itself.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919695","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":"Safety profiles of CAR-T cell therapy in systematic autoimmune diseases: a systematic review and analysis.","authors":"Yan Xie, Yang Liu, Xiaoyuan Chen, Qibing Xie","doi":"10.1007/s12026-026-09828-5","DOIUrl":"10.1007/s12026-026-09828-5","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptors (CARs)-T cell therapy is emerging as a potent approach for autoimmune diseases. However, its application in autoimmune conditions remains limited, and safety outcomes observed in malignancies can't reliably serve as a reference. Therefore, it's necessary to summarize the safety profiles in autoimmune diseases to provide evidence for future expanding trials.</p><p><strong>Methods: </strong>A systematic review was conducted to analyze the CAR-T therapy safety in rheumatic diseases via database searches up to December 2025. Studies reporting safety data were included, while abstracts, reviews, and cases with malignancies were excluded. Factors associated with cytokine release syndrome (CRS) were analyzed using Firth's penalized logistic regression.</p><p><strong>Results: </strong>This study included 38 studies, involving a total of 115 patients with autoimmune disease. Severe adverse events were rare. CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 70.4% and 4.3% of patients, respectively. Most CRS were low-grade. Multivariate analysis identified BCMA-targeted therapy and allogeneic CAR-T products may as independent factors associated with a reduced risk of CRS. Transient hematologic toxicity and hypogammaglobulinemia were frequently reported, with infections occurring in nearly half of the patients. However, prolonged cytopenia and severe infection were infrequent.</p><p><strong>Conclusion: </strong>Based on the current available evidence, CAR-T therapy appears to have a generally manageable safety profile in autoimmune diseases, supporting its potential as a promising treatment option for patients with relapsed or refractory autoimmune diseases. However, these findings remain preliminary, and further expanded studies are warranted in the future to provide higher-level evidence.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911853","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":"USP19 facilitates CSE-induced cell damage and ferroptosis in chronic obstructive pulmonary disease by deubiquitinating HDAC6 to drive PRDX6 deacetylation.","authors":"Yingbo Yang, Jianmei Guo, Xiaoli Fu, Bolan Chai","doi":"10.1007/s12026-026-09835-6","DOIUrl":"10.1007/s12026-026-09835-6","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow obstruction. Peroxiredoxin 6 (PRDX6) is vital in antioxidant defense and phospholipid metabolism, and linked to disease occurrence and progression. Ubiquitin-specific protease 19 (USP19), a deubiquitinating enzyme involved in protein stability regulation, has been implicated in inflammatory diseases and cellular stress responses, yet its role in COPD remains largely unknown. The objective of this study is to investigate the impact and the underlying mechanism of PRDX6 on cigarette smoke extract (CSE)-induced cell injury and ferroptosis, with a focus on the regulatory roles of USP19 and histone deacetylase 6 (HDAC6).</p><p><strong>Methods: </strong>The expression levels of the genes were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and western blot. The Cell counting kit-8 (CCK-8) was utilized to assess cell viability. Cell apoptosis was detected by flow cytometry. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected using the enzyme-linked immunosorbent assay (ELISA). The iron ion (Fe2+), reactive oxygen species (ROS), and glutathione (GSH) kits were used to evaluate the ferroptosis index. The Biological General Repository for Interaction Datasets (BioGRID), Hitpredict database, and Ubibrowser database were used to predict protein interactions. Protein modifications and protein-protein interactions were verified using co-immunoprecipitation (CoIP). The treatment with cycloheximide (CHX) was used to verify protein stability. The rat COPD model was used for in vivo validation. Hematoxylin-eosin (HE), Masson's trichrome (Masson) and Periodic Acid-Schiff (PAS) staining were utilized for the assessment of lung injury. Immunohistochemistry (IHC) analysis was conducted to assess the levels of PRDX6 present in rat lung tissue.</p><p><strong>Results: </strong>In CSE-induced 16HBE cells, upregulating PRDX6 expression mitigated the decline in cellular viability, prevented apoptosis, suppressed inflammatory reactions, and halted ferroptosis. HDAC6 facilitated CSE-induced cellular damage and ferroptosis by mediating the deacetylation modification of PRDX6. USP19 enhanced the stability of HDAC6 by deubiquitination, thereby exacerbating CSE-induced cellular damage and ferroptosis. The elevated levels of PRDX6 mitigated cellular damage and ferroptosis in the rat COPD models.</p><p><strong>Conclusions: </strong>USP19 modulates PRDX6 expression by deubiquitinating HDAC6, thereby promoting CSE-induced cellular damage and ferroptosis. This deepens our understanding on COPD pathogenic mechanism and may offer a new perspective for COPD treatment.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911820","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":"Deep learning for automated classification of antinuclear antibody patterns on HEp-2 indirect immunofluorescence images.","authors":"Altan Akıneden, Rayan Abri, Fatih Mehmet Akıllı, Sara Abri, Selçuk Türkel, Beste Akıllı, Emre Avuçlu, Yücel Duman","doi":"10.1007/s12026-026-09841-8","DOIUrl":"10.1007/s12026-026-09841-8","url":null,"abstract":"<p><p>Standardizing the interpretation of ANA patterns is a persistent challenge in rheumatology due to inter-observer discordance. This research introduces an ensemble deep learning framework optimized for the International Consensus on ANA Patterns (ICAP) system. By integrating ResNet-50 and EfficientNet-B0 via validation-tuned weighting and logit-level averaging, we processed both a single-label benchmark and a high-variability clinical dataset containing overlapping (multi-label) patterns. Our model demonstrated high fidelity in the single-label setting (92.5% accuracy; MCC = 0.9193). Critically, in the independent hospital cohort, the system managed the complexities of co-occurring patterns with a 1.26% Hamming loss and a micro F1-score of 82.91%. By achieving \"near-miss\" accuracy (within two labels) in over 95% of clinical cases, this framework demonstrates its potential utility as a decision-support tool that may help mitigate the inherent variability associated with manual HEp-2 cell analysis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911865","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":"Clinical and immunological characterization of a child with a homozygous TBK1 kinase-domain truncation.","authors":"Busra Seniz Demir, Sumeyra Ozdemir Cicek, Mohammad Ahmad Houran, Zehra Busra Azizoglu, Mine Asan, Hasan Bas, Benhur Sirvan Cetin, Hakan Gumus, Serife Erdem, Halit Canatan, Ekrem Unal, Elena Wy Hsieh, Aysenur Pac Kısaarslan, Ahmet Eken","doi":"10.1007/s12026-026-09838-3","DOIUrl":"10.1007/s12026-026-09838-3","url":null,"abstract":"<p><p>TBK1 is a serine-tyrosine kinase protein that transmits signals from pattern recognition receptors to the NF-κB pathway leading to production of Type 1 Interferons. Mutations in this protein have been associated with arthritis, vasculitis, herpes simplex encephalitis and amyotrophic lateral sclerosis. In the current study, we characterized the functional consequences of a TBK1-variant bearing a truncation in exon 4 and 5 in a patient with poly arthritis resembling juvenile idiopathic arthritis and necrotizing encephalitis. The truncation was associated with reduced TBK1 protein abundance and altered phosphorylation. The variant was associated with increased basal/and or Poly-I: C induced IL-6, TNFα, IL-1β and IL-18 and type 1 Interferon ex vivo. Our findings expand the phenotypic spectrum of TBK1 loss-of-function variants and may provide insight into the management of immune dysregulation in affected patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906022","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":"In vitro differentiation and phenotypic profiling of Langerhans cell subsets derived from human peripheral blood monocytes.","authors":"Sylwia Hasterok, Klas Berggren, Claes Af Klinteberg, Håkan Eriksson, Lars Ohlsson, Anna Gustafsson","doi":"10.1007/s12026-026-09825-8","DOIUrl":"10.1007/s12026-026-09825-8","url":null,"abstract":"<p><p>Langerhans cells (LCs) are primary immune sentinels at barrier surfaces, acting as the first line of defence against foreign pathogens. However, their low abundance within the human epidermis severely limits their availability for functional and mechanistic studies. To address this challenge, we sought to provide a versatile experimental framework for generating, identifying, and characterizing distinct subsets of LCs derived from in vitro differentiation of human peripheral monocytes. LCs' heterogeneity has long been considered, with recent studies classifying them into four subsets: effector LCs (LC1) and regulatory LCs (LC2) present at steady state, along with activated LCs (aLC) and migratory LCs (migLC) found during skin inflammation. In this study, LC1, LC2, and aLC/migLC subsets were identified by flow cytometric profiling of CD207, CD1a, CD83, and CD197. LC phenotype was further confirmed by examining HLA-DR, CD14, CD209, CD1b, and CD1c expression. Additionally, the phagocytic capacity of LCs relative to distinct macrophage polarizations was evaluated. From the in vitro-generated LCs, the subsets LC1, LC2, and a joint aLC/migLC cluster were identified. LC1 constituted the predominant population, appearing at higher proportions than both LC2 and the aLC/migLC cluster. The proportions of LC2 and aLC/migLC remained relatively consistent across donors, whereas LC1 abundance showed greater variation, suggesting a higher donor-dependent heterogeneity. Overall, LCs exhibited the lowest phagocytic capacity compared with the different macrophage polarizations. Our study defines LC subsets that can be generated from peripheral monocytes in vitro and provides a framework for deeper exploration of human LC biology, subset heterogeneity, and function in both normal and pathological skin.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906141","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":"SIX1 drives acute myeloid leukemia progression by reprogramming glycolytic metabolism and impairing CD8⁺ T-cell effector function.","authors":"Hui Hou, Ruijun Li, Lei Zhao, Yan Ma, Jingjing Zhao, Junli Li, Jianping Liu, Yumin Wang, Luqiang Zhang","doi":"10.1007/s12026-026-09803-0","DOIUrl":"10.1007/s12026-026-09803-0","url":null,"abstract":"<p><p>This study aimed to investigate the role of the homeobox gene SIX1 (sine oculis homeobox homolog 1) in acute myeloid leukemia (AML) progression and to explore its underlying metabolic and immunological mechanisms. SIX1 expression was examined in human bone marrow stromal cells (HS-5) and AML cell lines (HL-60, SKM-1, THP-1, KG-1, NB4, and MOLM13) using RT-qPCR. SIX1-knockdown and SIX1-overexpressing MOLM13 cells were generated by RNA interference and plasmid transfection, respectively. Cell cycle distribution, proliferation, and metabolic parameters, including intracellular glucose, lactate, and ATP levels, were assessed using flow cytometry, EdU incorporation, MTT assays, and ELISA. Mitochondrial content was analyzed by transmission electron microscopy. Peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with genetically modified MOLM13 cells under low-glucose conditions to evaluate T-cell proportions and cytokine production (IL-6, TNF-α, and IFN-γ). An AML mouse model was further established to assess the effects of SIX1 on T-cell composition and function by flow cytometry, while global metabolomics was applied to characterize metabolic reprogramming in vivo. SIX1 was significantly up-regulated in AML cells and promoted MOLM13 cell proliferation by enhancing glycolytic metabolism. Moreover, SIX1 suppressed CD8⁺ T-cell effector function both in vitro and in vivo and was associated with extensive alterations in amino acid, glucose, and lipid metabolism in AML mice. SIX1 facilitates AML progression by promoting glycolytic reprogramming in leukemia cells and potentially impairing CD8⁺ T-cell effector function through metabolic competition, highlighting SIX1 as a promising therapeutic target.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887395","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}