Frontiers in Immunology最新文献

{"title":"Advancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer.","authors":"Lijuan Qin, Yuan Li, Juan Liu, Xiaoqin An","doi":"10.3389/fimmu.2025.1554256","DOIUrl":"10.3389/fimmu.2025.1554256","url":null,"abstract":"<p><p>Immunotherapy has revolutionized cancer treatment, offering hope for patients with otherwise treatment-resistant tumors. Among the most promising approaches are cellular therapies, particularly chimeric antigen receptor T-cell (CAR-T) therapy, which has shown remarkable success in hematologic malignancies. However, the application of these therapies to solid tumors, such as lung and colorectal cancers, has faced significant challenges. Tumor resistance mechanisms-ranging from immune evasion, antigen loss, and immune checkpoint upregulation, to tumor microenvironment immunosuppression-remain major obstacles. This mini-review highlights the latest advancements in tumor immunotherapy, with a focus on cellular therapies, and addresses the resistance mechanisms that hinder their effectiveness in lung and colorectal cancers. We examine the evolution of CAR-T cell therapy, as well as the potential of engineered natural killer (NK) cells and macrophages in solid tumor treatment. The review also explores cutting-edge strategies aimed at overcoming resistance, including combination therapies, gene editing technologies, and nanotechnology for targeted drug delivery. By discussing the molecular, cellular, and microenvironmental factors contributing to resistance, we aim to provide a comprehensive overview of how these challenges can be overcome, paving the way for more effective, personalized immunotherapies in lung and colorectal cancer treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1554256"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory B cells and their transcriptomic profiles associated with belimumab resistance in systemic lupus erythematosus in the maintenance phase.","authors":"Takeshi Iwasaki, Hajime Yoshifuji, Koji Kitagori, Shuji Sumitomo, Shuji Akizuki, Ran Nakashima, Hideaki Tsuji, Ryosuke Hiwa, Mirei Shirakashi, Kosaku Murakami, Akira Onishi, Hideo Onizawa, Masao Tanaka, Fumihiko Matsuda, Akio Morinobu, Koichiro Ohmura","doi":"10.3389/fimmu.2025.1506298","DOIUrl":"10.3389/fimmu.2025.1506298","url":null,"abstract":"<p><p>The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in the maintenance phase are unknown. Here, we collected blood samples from patients with SLE (n=44) treated with belimumab before and three and six months after treatment. RNA-Seq of whole blood was performed, and gene expression was quantified. Immune cell type enrichment analysis estimated immune cell subtype proportions and gene expression in each subtype. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) < 4 at six months was set as the primary efficacy criterion. Non-responders exhibited upregulated B cell proliferation signals before treatment, associated with an increased number of memory B cells. A higher proportion of memory B cells before treatment predicted poor response (<i>p</i>=5.1×10^-4). This was also associated with changes in disease activity and glucocorticoid dose at six months compared with baseline. Belimumab did not affect memory B cell proportion during the treatment time course, in contrast to naïve B cells. Higher memory B cell proportion was associated with higher type-I interferon (IFN) scores and lower white blood cell and complement C4 levels. Transcriptomic analysis of memory B cells in non-responders revealed significant upregulation of immunoglobulin genes (Ig). Memory B cells and high Ig expression in them were identified as a treatment-resistant factor of belimumab in SLE patients. Lower C4 and white blood cell counts may serve as clinical markers of higher memory B cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1506298"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dental problems and oral microbiome alterations in ulcerative colitis.","authors":"Robert Kucharski, Bartosz Kamil Sobocki, Ewa Stachowska, Nikola Bulman, Leszek Kalinowski, Karolina Kaźmierczak-Siedlecka","doi":"10.3389/fimmu.2025.1502605","DOIUrl":"10.3389/fimmu.2025.1502605","url":null,"abstract":"<p><p>Ulcerative colitis is a chronic disease that has not well-established etiology. The role of microbial dysregulation in its pathogenesis has been recently highlighted. Overall, microbiome alterations concern the reduction of bacterial abundance and diversity, resulting in gut microbiome imbalance negatively affecting immunological aspects. There is a link between ulcerative colitis and the oral microbiome. The changes of oral microbiome are found at many levels, from gently dysbiotic composition to the presence of the main periodontal microbes. The analysis of oral microbiome can be a part of personalized medicine due to the fact that it is a potential biomarker. Patients with ulcerative colitis may manifest dental symptoms/problems, such as periodontitis (strongly related to the red-complex pathogens-<i>Porphyromonas gingivalis</i>, <i>Tannerella forsythia</i>, <i>Treponema denticola</i>, and bacteria belonging to the other complexes, such as <i>Fusobacterium nucleatum</i> and <i>Aggregatibacter actinomycetecomitans</i>), dental caries, oral ulcerations, leukoplakia, halitosis, and others. Notably, the DMFT (Decayed, Missing, Filled Teeth) index is higher in these patients compared to healthy subjects. According to some data, oral lichen planus (which is a disease with an immunological background) can also be observed in ulcerative colitis patients. It seems that deep understanding of ulcerative colitis in association with oral microbiome, immunology, and dental manifestations may be crucial to provide complex treatment from a dental point of view.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1502605"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchus-associated lymphoid tissue in lung transplantation: a facilitator of rejection or regulator of tolerance?","authors":"Alexander N Wein, Charles R Liu, Daniel Kreisel","doi":"10.3389/fimmu.2025.1553533","DOIUrl":"10.3389/fimmu.2025.1553533","url":null,"abstract":"<p><p>The role of bronchus-associated lymphoid tissue (BALT) in the regulation of immune responses to transplanted lungs remains an area of interest and controversy. Early studies in a rat pulmonary transplant model suggested BALT may accelerate rejection of grafts by inducing a local and systemic inflammatory response. Such observations were corroborated in intrapulmonary tracheal transplant models in the rat. While some human studies have described the presence of BALT in grafts that have been chronically rejected, others did not observe an association between induction of BALT and adverse outcomes. More recent investigations have found that BALT, enriched in immunoregulatory cell populations, is induced in tolerant mouse lung allografts, suggesting that such structures may be protective against rejection. Thus, the role of BALT in lung transplantation biology is complex. Insights gained from studies that focus on the role of BALT in lung transplantation may be harnessed to develop new therapies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1553533"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic characterization of STING expression in hematological malignancies reveals association with prognosis and anti-tumor immunity.","authors":"Xiang-Mei Wen, Zi-Jun Xu, Ji-Chun Ma, Min-Jie Zhang, Ye Jin, Jiang Lin, Jun Qian, Yuan-Yuan Fang, Shu-Yu Luo, Zhen-Wei Mao","doi":"10.3389/fimmu.2025.1477100","DOIUrl":"10.3389/fimmu.2025.1477100","url":null,"abstract":"<p><strong>Introduction: </strong>Stimulator of interferon response cGAMP interactor (STING) is essential for both innate and adaptive immunity. However, a comprehensive molecular characterization of STING expression across hematological malignancies is lacking.</p><p><strong>Methods: </strong>In this study, the pan-blood-cancer landscape related to STING expression was identified using the GTEx, CCLE, Hemap, and TCGA databases, and the potential value for predicting prognosis was investigated. The relationship between STING expression and immune cell enrichment was assessed in the Hemap database. Moreover, the value of STING in predicting the efficacy of immunotherapy was validated using tumor immune dysfunction and exclusion (TIDE) biomarkers and real-world immunotherapy datasets.</p><p><strong>Results and discussion: </strong>STING was found to be relatively highly expressed in acute myeloid leukemia (AML) and chronic myeloid leukemia, with higher STING expression correlated with poorer prognosis in AML. STING expression was positively correlated with immune-related pathways such as IFN-gamma response, IFN-alpha response, and inflammatory response. Cytolytic score and STING expression were positively correlated in some hematological tumors, especially chronic lymphocytic leukemia and mantle cell lymphoma. Interestingly, STING expression was negatively correlated with TIDE biomarkers in AML, suggesting that AML patients with a high STING expression level may benefit from immunologic treatment. Our findings contribute a molecular characterization of STING across hematological malignancies, facilitating the development of individualized prognosis and treatment strategies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1477100"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes secreted by ATF3/Nrf2-mediated ferroptotic renal tubular epithelial cells promote M1/M2 ratio imbalance inducing renal interstitial fibrosis following ischemia and reperfusion injury.","authors":"Qiao Tang, Jiatao Xie, Yifei Wang, Chong Dong, Qian Sun","doi":"10.3389/fimmu.2025.1510500","DOIUrl":"10.3389/fimmu.2025.1510500","url":null,"abstract":"<p><strong>Background: </strong>Severe renal ischemia and reperfusion injury (IRI) progresses to renal interstitial fibrosis (RIF) with limited therapeutic strategies. Although ferrptosis and macrophage polarization both play important roles in this model, their specific pathogenesis and interactions have not been elucidated. Therefore, we aimed to explore the mechanisms by which ferrotosis occurs in renal tubular epithelial cells (RTECs) and ferroptotic cell-derived exosomes induce macrophage polarization in IRI-related RIF model.</p><p><strong>Methods: </strong><i>In vivo</i>, C57BL/6J mice were randomly divided into four groups: sham group, ischemia and reperfusion (IR) group, IR + Ferrostatin-1 (Fer-1) group, and IR +ATF3 knockdown (ATF^KD) group. <i>In vitro</i>, RTECs were divided into control (CON) group, hypoxia/reoxygenation (HR) group, HR +Fer-1 group, HR + siRNA-ATF3 (siATF3) group.</p><p><strong>Result: </strong>Compared with the sham group, the IR group showed more severe kidney injury in HE staining, more collagen fibers in Masson staining, and higher α-SMA expression levels in immunohistochemistry. Total iron and MDA content increased while GSH content decreased. The IR group had more significant mitochondrial damage and higher PTGS2 and TFRC mRNA levels than those in the sham group. Compared with the IR group, the above indexes were all alleviated in the IR+Fer-1 or IR+ATF3^KD groups. In addition, the protein expressions of ATF3, Nrf2 and HO-1 in the IR group were increased than those in sham group. Compared with the IR group, ATF3 expressions in the IR+Fer-1 or IR+ATF3^KD groups were decreased, and the protein contents of Nrf2 and HO-1 were further increased. Moreover, there were higher levels of M2 markers (Arg1, TGF-β and IL-10 mRNA) in the IR group than those in the sham group, and lower levels in the IR+Fer-1 group or in the IR+ATF3^KD group compared with the IR group. The results of <i>in vitro</i> experiment are consistent with those of <i>in vivo</i> experiment. Mechanistically, the release of exosomes carrying miR-1306-5p by the HR group promoted more M2 macrophage.</p><p><strong>Conclusion: </strong>ATF3 might accelerate the ferroptosis by inhibiting Nrf2/ARE pathway, and exosomes from ferroptotic cells reduced the M1/M2 macrophage ratio, promoting fibrosis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1510500"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNβ drives ferroptosis through elevating TRIM22 and promotes the cytotoxicity of RSL3.","authors":"Huiyue Dong, Ling Zhu, Jingjing Sun, Qiuyan Chen, Pengyang Liu, Wei Zhang, Huajing Zeng, Rong Lin, Zongyang Yu, Jun Lu","doi":"10.3389/fimmu.2025.1535554","DOIUrl":"10.3389/fimmu.2025.1535554","url":null,"abstract":"<p><strong>Background: </strong>Cyclic GMP-AMP synthase (cGAS)-stimulator-of-interferon genes (STING) pathway is a cytosolic DNA sensor system. The production of this pathway, interferon-β (IFNβ), could suppress the growth of tumor cells, yet it is unclear whether ferroptosis is involved in IFNβ-induced cell death.</p><p><strong>Methods: </strong>The effects of IFNβ on ferroptosis were analyzed in HT1080, 4T1, HCT116 and 786-O cells. HT1080 and 4T1 cells treated with IFNβ were subjected to RNA-Seq analysis. STAT1, STAT3, TRIM21, and TRIM22 were silenced by siRNAs to examine their effects on IFNβ-induced ferroptosis. The cGAS-STING signaling pathway-activated mice were used to evaluate the effects of IFNβ on ferroptosis <i>in vivo</i>. HT1080 cells, three-dimensional (3D) spheroids, and the xenograft mouse models were treated with IFNβ, RSL3, or IFNβ combination with RSL3 to analyze whether IFNβ enhances RSL3-induced ferroptosis.</p><p><strong>Results: </strong>Here, we found that IFNβ could promote intracellular Fe²⁺ and lipid peroxidation levels, and decrease GSH levels in tumor cells. RNA sequencing data revealed that IFNβ induced a transcriptomic disturbance in ferroptosis-related genes. Knockdown of tripartite motif-containing 22 (TRIM22) suppressed the levels of intracellular Fe²⁺ and lipid ROS. It also reduced heme oxygenase (HMOX1) protein levels and increased ferroptosis suppressor protein 1 (FSP1) levels in HT1080 cells treated with IFNβ. Furthermore, our results illustrated that IFNβ enhanced the RAS-selective lethal 3 (RSL3)-induced ferroptosis and the inhibitory effect of RSL3 on GPX4. Meanwhile, compared to the groups treated with either IFNβ or RSL3 alone, the combination treatment of IFNβ and RSL3 significantly inhibited the growth of HT1080 three-dimensional (3D) spheroids and tumor in a mouse xenograft model.</p><p><strong>Conclusions: </strong>Our work reveals a role for IFNβ in promoting ferroptosis and provides evidence that IFNβ could be used with RSL3 to increase cytotoxic effects in tumor cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1535554"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron and ferroptosis in kidney disease: molecular and metabolic mechanisms.","authors":"Wenjie Wang, Jingdi Chen, Liying Zhan, Handong Zou, Lu Wang, Mengmeng Guo, Hang Gao, Jing Xu, Wei Wu","doi":"10.3389/fimmu.2025.1531577","DOIUrl":"10.3389/fimmu.2025.1531577","url":null,"abstract":"<p><p>Maintaining iron homeostasis is necessary for kidney functioning. There is more and more research indicating that kidney disease is often caused by iron imbalance. Over the past decade, ferroptosis' role in mediating the development and progression of renal disorders, such as acute kidney injury (renal ischemia-reperfusion injury, drug-induced acute kidney injury, severe acute pancreatitis induced acute kidney injury and sepsis-associated acute kidney injury), chronic kidney disease (diabetic nephropathy, renal fibrosis, autosomal dominant polycystic kidney disease) and renal cell carcinoma, has come into focus. Thus, knowing kidney iron metabolism and ferroptosis regulation may enhance disease therapy. In this review, we discuss the metabolic and molecular mechanisms of iron signaling and ferroptosis in kidney disease. We also explore the possible targets of ferroptosis in the therapy of renal illness, as well as their existing limitations and future strategies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1531577"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration.","authors":"Lucas Stürzbecher, Hendrik Bartolomaeus, Theda U P Bartolomaeus, Sylvia Bolz, Andjela Sekulic, Marius Ueffing, Simon J Clark, Nadine Reichhart, Sergio Crespo-Garcia, Nicola Wilck, Olaf Strauß","doi":"10.3389/fimmu.2025.1520188","DOIUrl":"10.3389/fimmu.2025.1520188","url":null,"abstract":"<p><strong>Introduction: </strong>Age-related macular degeneration (AMD) is a leading cause of blindness with limited treatment options. Dysfunction of the retinal pigment epithelium (RPE) is a unifying salient feature of the pathology and a primary end-point damage leading to complications such as geographic atrophy (GA), which represents the most common end-stage of AMD.</p><p><strong>Methods: </strong>Human and murine ocular tissues were used for histological examinations. Furthermore, flow cytometry and gene expression analysis were used on ocular and splenic tissues of <i>Cx3cr1</i> ^GFP/GFP and <i>C57BL/6J</i> mice at 8 and 12 months of age to characterize the dynamics of local and systemic T cell populations.</p><p><strong>Results: </strong>We show the presence of memory T cells such as CD45RO⁺ cells in the choroid and retina of patients with AMD with a peak of abundance in early stages of AMD. As further evidence for the contribution of the adaptive immune system to GA we identified an increased frequency of CD44⁺ CD69⁺ KLRG1⁺ T cells and para-inflammation of the retina in a mouse model that mimics features of GA. Importantly, the activation of T cells found at early AMD-like stages prior to degeneration possessed long-lasting cytotoxic properties and adopted typical features of senescent immune cells. T cells were intimately associated with the RPE, suggesting transmigration and participating in local micro-inflammation.</p><p><strong>Discussion: </strong>Our data support that activation and accumulation of memory T cells can be considered as a hallmark of early AMD, and that adaptive immunosenescence likely to contribute to the chronic inflammation associated with RPE damage and the progression to large lesions as seen in GA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1520188"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in immunosuppression-related genes are associated with AML.","authors":"Mingying Li, Jingjing Ye, Mengyuan Chang, Lei Feng, Tingting Liu, Di Zhang, Yuyan Wu, Yuechan Ma, Guangqiang Meng, Chunyan Ji, Tao Sun","doi":"10.3389/fimmu.2025.1530510","DOIUrl":"10.3389/fimmu.2025.1530510","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a hematologic malignancy with poor overall survival (OS). The immunosuppressive microenvironment significantly impacts AML development and chemoresistance. Despite new immunotherapeutic strategies entering standard clinical care for various tumors, progress in AML remains poor. Multi-omics analyses, such as single-cell transcriptomics, have revealed many potential new targets to improve AML prognosis from an immunological perspective.</p><p><strong>Methods: </strong>DNA from 307 AML patients and 316 healthy individuals were extracted. We detected nine single nucleotide polymorphisms (SNPs) in five immunosuppression-related genes (CIITA, CD200, CD163, MRC1 and LILRB4) in these samples. SNP genotyping was performed on the MassARRAY platform. We then analyzed the relationship between these SNPs and AML susceptibility, treatment response, and prognosis.</p><p><strong>Results: </strong>Our findings indicated that rs4883263 in the CD163 gene is a protective factor for AML susceptibility and chromosomal karyotype abnormalities. Additionally, rs4883263 in CD163 was related to low PLT count at diagnosis, while rs2272022 in CD200 was protective against low PLT count. rs4780335 in CIITA was associated with high WBC count at diagnosis and worse OS. Furthermore, rs1048801 in LILRB4 was linked to worse AML treatment response, lower OS, and may be an independent prognostic risk factor for AML. Lastly, expressions of CD163, CIITA, LILRB4, and CD200 were higher in AML patients than that in normal controls.</p><p><strong>Conclusions: </strong>Our findings on SNP associations in AML immunosuppression-related genes provide important reference points for predicting treatment outcomes in AML patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1530510"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}