Immunological Investigations最新文献_第8页

The IL 12 Cytokine Family in Cardiovascular Disease: Context Dependent Signaling, Immune Remodeling, and Therapeutic Implications. 心血管疾病中的IL - 12细胞因子家族：环境依赖性信号、免疫重塑和治疗意义

IF 2.4 4区医学

Immunological Investigations Pub Date : 2026-06-02 DOI: 10.1080/08820139.2026.2680482

Xing Meng, Chao Wang

{"title":"The IL 12 Cytokine Family in Cardiovascular Disease: Context Dependent Signaling, Immune Remodeling, and Therapeutic Implications.","authors":"Xing Meng, Chao Wang","doi":"10.1080/08820139.2026.2680482","DOIUrl":"https://doi.org/10.1080/08820139.2026.2680482","url":null,"abstract":"Cardiovascular diseases (CVDs) are increasingly recognized as immune-mediated disorders in which cytokines regulate leukocyte recruitment, activation, and tissue repair. This review summarizes the roles of the interleukin-12 (IL-12) cytokine family, including IL-12, interleukin-23 (IL-23), interleukin-27 (IL-27), and interleukin-35 (IL-35), in vascular and myocardial pathology. We highlight the heterodimeric structure and shared-subunit biology of these cytokines, which produce overlapping receptor usage and downstream Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling, contributing to substantial functional pleiotropy. Mechanistic evidence is reviewed showing how IL-12 family cytokines regulate endothelial activation, adhesion pathways, leukocyte recruitment, macrophage polarization, and immune-stromal crosstalk, thereby influencing extracellular matrix turnover and cardiovascular remodeling. Disease-specific findings are discussed in atherosclerosis, angiotensin II-associated hypertension, myocardial infarction, pulmonary hypertension, and diabetic cardiomyopathy. Across these conditions, cytokines may exert either protective or pathogenic effects depending on timing, cellular source, receptor context, and tissue environment. We further examine translational implications for biomarker development and therapeutic targeting, emphasizing the challenge of distinguishing prognostic associations from causal signaling. Overall, IL-12 family cytokines act as context-dependent immunoregulatory nodes in CVD.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-25"},"PeriodicalIF":2.4,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149633","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}

引用次数: 0

Reduced miR-193a-3p Modulates Cell Proliferation and Apoptosis in Inflammatory Bowel Disease via Targeting ETS1. 降低miR-193a-3p通过靶向ETS1调节炎症性肠病的细胞增殖和凋亡

IF 2.4 4区医学

Immunological Investigations Pub Date : 2026-05-27 DOI: 10.1080/08820139.2026.2677601

Hailin Cheng, Lei Xiao, Tao Xu

{"title":"Reduced miR-193a-3p Modulates Cell Proliferation and Apoptosis in Inflammatory Bowel Disease via Targeting ETS1.","authors":"Hailin Cheng, Lei Xiao, Tao Xu","doi":"10.1080/08820139.2026.2677601","DOIUrl":"https://doi.org/10.1080/08820139.2026.2677601","url":null,"abstract":"Background: Multiple findings have demonstrated that microRNAs (miRNAs) have a profound impact on inflammatory bowel disease (IBD) pathogenesis. This research was conceived to elucidate the regulatory function of miR-193a-3p in IBDby targeting ETS proto‑oncogene 1 and explore its potential diagnostic value.Methods: Expression of miR-193a-3p was determined by reverse transcription quantitative real‑time polymerase-chain reaction (RT‑qPCR). Cell viability, apoptosis, and inflammatory responses were measured in lipopolysaccharide (LPS)-stimulated human normal colonic epithelial FHC cells using the cell counting kit‑8 (CCK‑8) assay, flow cytometry, and enzyme‑linked immunosorbent assay (ELISA), respectively. The dual-luciferase reporter's assay verified the targeting relationship.Results: miR-193a-3p was downregulated whereas ETS1 was upregulated in patients with inflammatory bowel disease (IBD). Its expression was negatively correlated with IBD severity in both ulcerative colitis (UC) and Crohn's disease (CD). In vitro, elevated miR-193a-3p alleviated LPS-induced inflammation and apoptosis and promoted cell proliferation. A negative regulatory relationship between miR-193a-3p and ETS1 was validated experimentally. miR-193a-3p overexpression inhibited LPS-mediated upregulation of ETS1. In addition, ETS1 overexpression suppressed cell proliferation and facilitated inflammation and cell apoptosis.Conclusion: miR-193a-3p was involved in the pathogenesis of IBD by directly targeting ETS1.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-19"},"PeriodicalIF":2.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029738","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}

引用次数: 0

Immune Checkpoints in Sepsis and the Path Toward Precision Immunotherapy. 脓毒症的免疫检查点和精确免疫治疗的途径。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-03-14 DOI: 10.1080/08820139.2026.2644292

Bilal Abbas, Arshad Abbas, Iqbal Nawaz Khan

{"title":"Immune Checkpoints in Sepsis and the Path Toward Precision Immunotherapy.","authors":"Bilal Abbas, Arshad Abbas, Iqbal Nawaz Khan","doi":"10.1080/08820139.2026.2644292","DOIUrl":"10.1080/08820139.2026.2644292","url":null,"abstract":"Background/objective: Sepsis remains a leading cause of mortality worldwide, with immune dysfunction serving as a central driver of adverse outcomes. While early hyperinflammation contributes to organ damage, subsequent immunoparalysis characterized by T-cell exhaustion, monocyte deactivation, and impaired pathogen clearance accounts for late deaths and susceptibility to secondary infections. Immune checkpoint molecules have emerged as critical mediators of sepsis-induced immunosuppression.Methods: We reviewed current literature on inhibitory checkpoint pathways including PD-1/PD-L1, CTLA-4, TIM-3, LAG-3, TIGIT, and BTLA in sepsis-induced immune dysfunction. Cell-type-specific expression patterns, dual protective and pathological roles of checkpoint signaling depending on timing and tissue context, and convergence with metabolic and epigenetic reprogramming sustaining immunoparalysis were analyzed. Myeloid checkpoints such as CD47-SIRPα and MerTK contributing to innate immune dysfunction were evaluated.Results: Checkpoint molecules exhibit context-dependent roles with protective and pathological effects varying by timing and tissue microenvironment. Monocyte HLA-DR and ferritin were identified as actionable biomarkers for patient phenotyping. The ImmunoSep trial provides proof-of-concept evidence demonstrating improved outcomes with phenotype-guided immunotherapy.Conclusions: Successful translation of checkpoint-based immunotherapies requires precision medicine frameworks matching the right intervention to the right patient at the right time. Combination immunotherapies hold promise when guided by biomarker-driven stratification.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"774-802"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456982","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}

引用次数: 0

Immunosuppressive Pulse Therapy Alleviates Ocular Surface Damage in Thyroid-Associated Ophthalmopathy by Reversing FGA Deficiency Subsequently Modulating Complement and Coagulation Cascade Signaling to Suppress Orbital Fibroblast Pathology. 免疫抑制脉冲疗法通过逆转FGA缺乏，随后调节补体和凝血级联信号抑制眼眶成纤维细胞病理，减轻甲状腺相关眼病的眼表损伤。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-02-25 DOI: 10.1080/08820139.2026.2627932

Xiaoqing Zhou, Qian Sha

{"title":"Immunosuppressive Pulse Therapy Alleviates Ocular Surface Damage in Thyroid-Associated Ophthalmopathy by Reversing FGA Deficiency Subsequently Modulating Complement and Coagulation Cascade Signaling to Suppress Orbital Fibroblast Pathology.","authors":"Xiaoqing Zhou, Qian Sha","doi":"10.1080/08820139.2026.2627932","DOIUrl":"10.1080/08820139.2026.2627932","url":null,"abstract":"Background: Thyroid-associated ophthalmopathy (TAO)is a common autoimmune inflammatory disorder that compromises visual function and quality of life. It is characterized by orbital tissue inflammation and ocular surface injury. Although immunosuppressive pulse therapy has shown clinical efficacy, its underlying molecular mechanisms remain incompletely understood.Methods: Tear samples were collected from 30 healthy controls and 30 patients with TAO before and after immunosuppressive pulse therapy. Proteomic profiling was performed using label-free quantitative liquid chromatography - tandem mass spectrometry (LC-MS/MS), and key proteins involved in FGA expression and complement-coagulation cascade signaling were validated by ELISA. Primary orbital fibroblasts (OFs) were isolated from TAO patients and subjected to FGA overexpression and immunosuppressant treatment. Fibrosis and adipogenic differentiation were assessed using a multidimensional approach, including CCK-8 assay, flow cytometry, Oil Red O staining, qRT-PCR, and Western blotting.Results: Immunosuppressive pulse therapy significantly alleviates ocular surface injury in TAO patients, primarily through FGA-mediated regulation of the complement and coagulation cascade pathway. Our findings identify FGA as a promising therapeutic target in TAO. Restoration of FGA expression synergizes with immunosuppressive therapy, highlighting a potential combinatory treatment strategy.Conclusion: FGA represents a potential therapeutic target for TAO. Enhancing FGA expression may augment the efficacy of immunosuppressive therapythrough synergistic modulationof inflammatory and fibrotic pathways.Clinical trial number: Not applicable.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"697-717"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305468","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}

引用次数: 0

The STING Signaling Pathway in Prostate Cancer: Mechanisms, Influencing Factors, and Therapeutic Strategies. 前列腺癌的STING信号通路：机制、影响因素和治疗策略。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-03-27 DOI: 10.1080/08820139.2025.2590048

Na Qu, Meng Zhang, Yating Ji, Mingxia Liu, Mengjiao Liu, Lijiang Chen

{"title":"The STING Signaling Pathway in Prostate Cancer: Mechanisms, Influencing Factors, and Therapeutic Strategies.","authors":"Na Qu, Meng Zhang, Yating Ji, Mingxia Liu, Mengjiao Liu, Lijiang Chen","doi":"10.1080/08820139.2025.2590048","DOIUrl":"10.1080/08820139.2025.2590048","url":null,"abstract":"Background: Prostate cancer (PCa) is a common malignancy in men globally. The cGAS-STING pathway shows promise in its treatment as it can enhance anti-tumor immunity and promote immunogenic cell death. However, the tumor microenvironment, with factors like immunosuppressive cells and gene regulatory factors, limits the efficacy of STING pathway activation.Objective: This review aims to systematically summarize the recent progress in targeting the cGAS-STING pathway for the treatment of prostate cancer.Methods: We first introduce the core mechanisms of STING signaling, and then explore its specific role in the pathogenesis and progression of prostate cancer. We analyze the key factors in the TME that limit STING activation, such as immunosuppressive cells and epigenetic regulators. In addition, we summarize the current strategies targeting STING, including STING agonists, combination therapies with immune checkpoint inhibitors, and radiotherapy-based approaches.Conclusion: Our analysis concludes that targeting the cGAS-STING pathway holds significant potential to overcome therapy resistance and improve outcomes in prostate cancer, although further research is needed to optimize its clinical application.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"803-832"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147528567","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}

引用次数: 0

The Progress of Tertiary Lymphoid Structures in Gastric Cancer. 胃癌三级淋巴结构的研究进展。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-03-31 DOI: 10.1080/08820139.2026.2622357

Fei Li, Wenjing Gong, Aina Liu

{"title":"The Progress of Tertiary Lymphoid Structures in Gastric Cancer.","authors":"Fei Li, Wenjing Gong, Aina Liu","doi":"10.1080/08820139.2026.2622357","DOIUrl":"10.1080/08820139.2026.2622357","url":null,"abstract":"Background: Tertiary lymphoid structures (TLSs), also known as ectopic lymphoid aggregates, have been increasingly recognized as important components of the tumor microenvironment. In gastric cancer, the presence, composition, size, density, and maturity of TLSs may significantly influence treatment response and patient prognosis.Objective: This review aims to summarize the formation of TLSs and evaluate their potential roles as prognostic biomarkers and therapeutic targets in gastric cancer.Methods: A comprehensive review of current literature was conducted to analyze the biological characteristics, formation mechanisms, and clinical relevance of TLSs in gastric cancer.Results: Evidence suggests that TLSs are closely associated with improved immune responses, better therapeutic outcomes, and favorable prognosis in gastric cancer. Their structural features and maturation status may further modulate their functional roles in antitumor immunity.Conclusion: TLSs represent promising prognostic indicators and potential targets for immunotherapy in gastric cancer. However, several challenges remain, and further research is needed to better understand their mechanisms and clinical applications, ultimately contributing to improved survival and quality of life in patients with advanced gastric cancer.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"833-851"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581286","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}

引用次数: 0

Unleashing the Potential of Anti-CD45RB Antibodies in Transplantation. 释放抗cd45rb抗体在移植中的潜力。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-02-03 DOI: 10.1080/08820139.2026.2622359

Yanling Zhang, Nan Li, Yachao Li

引用次数: 0

Differences in Shared T Cell receptor α Repertoire Associated with Recognition of Viral Antigens. 与病毒抗原识别相关的共享T细胞受体α库的差异

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-03-16 DOI: 10.1080/08820139.2026.2644288

Tiitus Lamponen, Joonatan Mattila, Nelli Heikkilä, Silja Sormunen, Jari Saramäki, T Petteri Arstila

{"title":"Differences in Shared T Cell receptor α Repertoire Associated with Recognition of Viral Antigens.","authors":"Tiitus Lamponen, Joonatan Mattila, Nelli Heikkilä, Silja Sormunen, Jari Saramäki, T Petteri Arstila","doi":"10.1080/08820139.2026.2644288","DOIUrl":"10.1080/08820139.2026.2644288","url":null,"abstract":"Background: Despite the high diversity of the αβ T cell receptor (TCR), sharing of identical TCR chains between individuals is common. This shared repertoire consists mainly of chains with few non-germline nucleotide additions. Many of these chains recognize conserved viral peptides, but it is unclear whether the number of nucleotide additions is similar regardless of specificity.Methods: We studied shared human TCR α chains associated with the recognition of viral antigens. The chains were retrieved from published databases. In sets of 6 thymus and 10 blood samples we identified these chains and analyzed their frequency and properties in the pre-immune and peripheral repertoire.Results: For all but one virus, the identified TCR α sequences conformed to the conventional public repertoire, with a high frequency of germline rearrangements and few nucleotide additions. Surprisingly, TCR α sequences associated with Herpes simplex virus 2 (HSV-2) displayed a bimodal division, with one group of sequences having a high number of inserts, while the other group was close to germline.Conclusion: Our results identify a novel type of shared TCR repertoire, likely to be generated by selection instead of convergent recombination. Whether this reflects features exclusive to the immune response against HSV-2 remains to be studied.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"718-733"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463243","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}

引用次数: 0

Propofol Exerted an Anti-Asthmatic Effect by Attenuating Extracellular Matrix Deposition and Viability of Airway Smooth Muscle Cells. 异丙酚通过降低气道平滑肌细胞的细胞外基质沉积和细胞活力而发挥抗哮喘作用。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-03-16 DOI: 10.1080/08820139.2026.2644290

Zhenzhen Chen, Yanyan Jiang, Hua Zhang, Xiaona An, Yuzhu Zhang, Lei Wei

{"title":"Propofol Exerted an Anti-Asthmatic Effect by Attenuating Extracellular Matrix Deposition and Viability of Airway Smooth Muscle Cells.","authors":"Zhenzhen Chen, Yanyan Jiang, Hua Zhang, Xiaona An, Yuzhu Zhang, Lei Wei","doi":"10.1080/08820139.2026.2644290","DOIUrl":"10.1080/08820139.2026.2644290","url":null,"abstract":"Introduction: Propofol is the preferred anaesthetic for asthma patients due to its bronchodilatory effects, yet its protective mechanisms remain unclear. This study investigated its effects both in vivo and in vitro.Methods: An asthmatic mouse model was induced using ovalbumin (OVA). Airway responsiveness, lung histopathology, and inflammatory biomarkers (IgE, IL-4, IFN-γ) were assessed. TGF-β1-stimulated airway smooth muscle (ASM) cells were used for proliferation, migration, and apoptosis assays via MTT, Transwell, and flow cytometry. ECM production was analyzed by immunohistochemistry and immunofluorescence. The SAPK/JNK signaling pathway was evaluated by western blot.Results: Propofol dose-dependently attenuated airway hyperresponsiveness and lung histological damage in OVA-induced asthmatic mice, while reversing abnormal inflammatory biomarker expression. In vitro, propofol inhibited ASM cell proliferation and migration and promoted apoptosis. It also suppressed ECM synthesis and restored TIMP-1 expression to rebalance ECM homeostasis. Mechanistically, propofol inhibited SAPK/JNK pathway activation in both in vivo and in vitro models.Discussion: These findings clarify the molecular mechanisms underlying Propofol's protective effects, providing a foundation for its potential therapeutic use in asthma treatment.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"734-749"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467900","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}

引用次数: 0

Astragalus Polysaccharide Promotes NLRP3⁺ Macrophages Polarization via Suppression of OGT in Hepatocellular Carcinoma. 黄芪多糖通过抑制肝癌细胞OGT促进NLRP3+巨噬细胞极化。

IF 2.3 4区医学

Immunological Investigations Pub Date : 2026-05-01 Epub Date: 2026-03-24 DOI: 10.1080/08820139.2026.2645964

Yaping Lv, Mingyun Ma, Xiaobo Zhu, Lingling Xv, Boqi Song, Pan Cheng, Qiang Huang, Chun Li

{"title":"Astragalus Polysaccharide Promotes NLRP3+ Macrophages Polarization via Suppression of OGT in Hepatocellular Carcinoma.","authors":"Yaping Lv, Mingyun Ma, Xiaobo Zhu, Lingling Xv, Boqi Song, Pan Cheng, Qiang Huang, Chun Li","doi":"10.1080/08820139.2026.2645964","DOIUrl":"10.1080/08820139.2026.2645964","url":null,"abstract":"Background: Hepatocellular carcinoma (HCC) is characterized by an immunosuppressive tumor microenvironment (TME) dominated by tumor-associated macrophages (TAMs). Astragalus polysaccharide (APS) exhibits anti-tumor activity, its mechanism in reprogramming immunosuppressive TAMs remains unclear.Methods: We established a subcutaneous HCC tumor model in C57BL/6 mice and administered APS. Single-cell RNA sequencing (scRNA-seq) was performed to profile immune cell landscapes in HCC TME. Flow cytometry, immunofluorescence, and functional assays were employed to explore the role of O-linked N-acetylglucosamine transferase (OGT) in APS-mediated TME reprogramming.Results: APS significantly inhibited tumor growth and remodeled the TME cellular composition. ScRNA-seq revealed 10 cell types in HCC mice tumor tissue. APS increased neutrophils, macrophages, and mast cells while reducing other immune populations. Macrophages were subclassified into C1QC+ TAM, NLRP3+ TAM, and S100A9+ TAM. APS specifically elevated NLRP3+ TAM abundance, which positively correlated with M1-like pro-inflammatory phenotypes (TNFα, complement pathway activation). Mechanistically, APS downregulated OGT expression and global O-GlcNAcylation in TAMs, promoting NLRP3+ TAM polarization. NLRP3+ TAMs with APS treatment secreted pro-inflammatory cytokines and chemokines (IL-6, IL-1B, TNFα, and CXCL10), enhancing CD8+ T-cell infiltration and reducing T-cell exhaustion.Conclusion: APS suppresses HCC by inhibiting OGT-mediated O-GlcNAcylation and promoting NLRP3+ M1-like TAMs enrichment, thereby enhancing anti-tumor immunity, highlighting APS as a potential immunomodulatory agent for HCC therapy.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"750-773"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511677","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}

引用次数: 0