Immunologic Research最新文献

{"title":"ASIA syndrome after BNT162b2 vaccination: Is it a distinct rheumatoid arthritis phenotype?","authors":"Mete Pekdiker, Sertaç Ketenci","doi":"10.1007/s12026-024-09540-2","DOIUrl":"https://doi.org/10.1007/s12026-024-09540-2","url":null,"abstract":"<p>Vaccines are an identified cause of autoimmune/inflammatory <i>syndrome</i> induced by adjuvants (ASIA syndrome). In this research, we aimed to investigate the remarkable features of patients, whom we classified as ASIA syndrome, developing rheumatoid arthritis (RA) after BNT162b2 vaccination. Patients who were asymptomatic before the BNT162b2 vaccination, developed chronic arthritis within 3 months after the vaccination, and fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism RA classification criteria were enrolled in the study. Demographic, laboratory, clinical, and treatment characteristics were reviewed retrospectively. We identified ten patients developing RA following BNT162b2 vaccination. The median age was 54.5 years and six of them were female. The median time between vaccination and onset of symptoms was 7 days; seven patients had acute arthritis, and four had intermittent arthritis at the onset of the disease. Only three patients had a disease onset in the small joints of the hands. All patients had radiological erosions on hand X-rays. We reported a case series of patients, classifiable as having ASIA syndrome, who developed RA with radiological erosions after the BNT162b2 vaccine. The onset of the disease in joints different from the typically expected ones, along with the early development of erosions in hand X-rays, suggests that these cases may follow a course distinct from classic RA. RA that develops following mRNA vaccination may have an aggressive course, but studies with larger sample sizes are needed.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261985","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":"Serum soluble interleukin-2 receptor alpha may predict tubulointerstitial inflammatory cell infiltration and short-term disease progression in immunoglobin A nephropathy","authors":"Chenqi Xu, Kunming Pan, Jie Li, Yang Li, Shi Jin, Yiqin Shi, Jie Teng, Xiaoqiang Ding, Xialian Xu, Hong Liu","doi":"10.1007/s12026-024-09533-1","DOIUrl":"https://doi.org/10.1007/s12026-024-09533-1","url":null,"abstract":"<p>This study aims to explore the relationship between serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels and histologic features in immunoglobin A nephropathy (IgAN), and evaluate its predicting values on disease progression and remission status. IgAN patients were included retrospectively. Lee classification, Oxford classification and histological scoring were evaluated. Patients’ estimated filtration rate (eGFR) and proteinuria remission status were collected during 6-month follow-up. Logistic regression was used to determine the risk factors and predicting value. Receiver operating characteristic (ROC) curve were used to determine the predicting value for outcome. One hundred seventy-two subjects were included in this study. Individuals in moderate-to-severe tubulointerstitial inflammatory cell infiltration group manifested with significantly elevated serum sIL-2Rα levels than those in non-to-mild group. Serum sIL-2Rα levels were positively correlated with infiltration scores. Serum sIL-2Rα was an independent risk factor for moderate-to-severe inflammatory cell infiltration [sIL-2Rα: OR 1.29 (1.015–1.640, <i>p</i> = 0.038)]. ROC curve analysis regarding predictive value for moderate-to-severe inflammatory cell infiltration of sIL-2Rα suggested area under curve was 0.859 (0.801–0.918, <i>p</i> = 0.000) when sIL-2Rα combined with eGFR &lt; 60 mL/(min·1.73 m²), 24-h proteinuria excretion &gt; 1.0 g, and hemoglobin. It showed good sensitivity (71.6%) and specificity (87.6%). Additionally, sIL-2Rα levels at kidney biopsy were strong predictive factor for kidney function loss 6 months after kidney biopsy [OR 4.161 (1.013–17.088, <i>p</i> = 0.048)]. High serum sIL-2Rα was significantly associated with serious inflammatory cell infiltration in IgAN, and it showed strong predictive value for disease prognosis. Serum sIL-2Rα could be a useful noninvasive biomarker to evaluate the extent of histological injury and disease prognosis in IgAN.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261987","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":"Tumour-associated macrophages in diffuse large B-cell lymphoma: the prognostic and therapeutic impact in a South African centre with high HIV seroprevalence","authors":"Jenifer Vaughan, Tracey Wiggill, Zainab Mia, Moosa Patel","doi":"10.1007/s12026-024-09537-x","DOIUrl":"https://doi.org/10.1007/s12026-024-09537-x","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is a common malignancy among people living with HIV. Macrophage enrichment of the tumour microenvironment (TME) is a prognostic factor in DLBCL among immunocompetent people, with some studies reporting that macrophage enrichment predicts a superior response to rituximab therapy. The macrophage phenotype is also important, with reportedly poorer outcomes with enrichment of anti-inflammatory (M2) macrophages. To date, the relationship between the type/number of tumour macrophages and outcomes in HIV-associated DLBCL (HIV-DLBCL) has been poorly explored. In this study, we assessed tumour macrophage numbers in a South African cohort of patients with DLBCL and a high HIV-seropositivity rate. Immunohistochemistry for CD68 and CD163 was performed on the diagnostic biopsies of 79 patients with DLBCL. Relevant information was documented from the clinical records, including disease stage, international-prognostic index score, HIV-related parameters, C-reactive protein, ferritin levels and immune cell numbers (monocytes, lymphocytes and neutrophils). Survival analysis was performed using Kaplan–Meier survival estimates, and the correlation between tumour macrophage numbers and a variety of immunological parameters was assessed using Spearman’s rho. Of the 79 patients included, 87.2% were living with HIV, and rituximab therapy was used in 46.9%. Tumour macrophage numbers were not related to HIV status, but low pro-inflammatory (M1) macrophage numbers (CD68 + CD163 −) were significantly associated with poorer outcomes (HR 2.02, <i>p</i> = 0.03). M2 macrophage (CD68 + CD163 +) enrichment was not predictive of survival but was associated with improved response to rituximab therapy (HR 0.19; <i>p</i> = 0.002). Macrophage numbers were marginally correlated with ferritin levels, which showed modest performance as a peripheral blood biomarker of the TME macrophage status (AUC 0.6 at a level of 374 µg/L), and high ferritin levels were associated with a superior response to rituximab-therapy (HR 0.28, <i>p</i> = 0.034). Pro-inflammatory macrophages are important in tumour control in HIV-DLBCL, while M2 macrophage enrichment improves the response to rituximab therapy. Ferritin shows promise as a biomarker for identifying patients more likely to benefit from rituximab therapy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187196","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":"Changes in immune subsets during chemotherapy as prognosis biomarkers for multiple myeloma patients by longitudinal monitoring","authors":"Pengcheng Xu, Ying Li, Xibing Zhuang, Lei Yue, Yanna Ma, Wenjin Xue, Lili Ji, Yanxia Zhan, Yang Ou, Tiankui Qiao, Duojiao Wu, Peng Liu, Hao Chen, Yunfeng Cheng","doi":"10.1007/s12026-024-09521-5","DOIUrl":"https://doi.org/10.1007/s12026-024-09521-5","url":null,"abstract":"<p>Multiple myeloma (MM) is a malignancy of plasma cells accompanied by immune dysfunction. This study aimed to provide a comprehensive and dynamic characterization of the peripheral immune environment in MM patients and find its diagnostic and prognostic values for therapy. The peripheral immune profiles of MM inpatients and healthy controls were assessed by flow cytometry. A longitudinal study of immune subsets was observed during cycles of chemotherapy. The diagnostic and prognostic models were established based on immune subsets by the absolute shrinkage and selection operator (LASSO) and multivariate regression. MM patients possessed an impeded immune landscape, including reduced activation of B cells, increased effective T cells and regulatory T cells (Tregs), augmented CD16 expression on monocytes and dendritic cell percentages, decreased CD56^dimCD16⁺ natural killer cells (NKs), and amplified CD56^bright and HLA-DR⁺ natural killer T cells (NKTs). Chemotherapy has different dynamic effects on specific cells, of which 2 cycles is the key turning point. NKT, dendritic cells, naïve Tc and Th cells, HLA-DR⁺ Tc cells, CD56^dim NKTs, CD16⁺⁺ monocytes, and CD25⁺ B cells could have the diagnostic value, and a prognostic model including neutrophils, naïve Tc cells, CD56^brightCD16^dim NKs, and CD16⁺ dendritic cells was established with acceptable accuracy. Our data showed dynamic and abnormal peripheral immune profiles in MM patients, which had prognostic values and could provide the basis for clinical therapy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187197","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":"NK/DC crosstalk-modulating antitumor activity via Sema3E/PlexinD1 axis for enhanced cancer immunotherapy.","authors":"Awais Ali, Abdulaziz Alamri, Azraida Hajar","doi":"10.1007/s12026-024-09536-y","DOIUrl":"https://doi.org/10.1007/s12026-024-09536-y","url":null,"abstract":"<p><p>The complex relationship between natural killer (NK) cells and dendritic cells (DCs) within the tumor microenvironment significantly impacts the success of cancer immunotherapy. Recent advancements in cancer treatment have sought to bolster innate and adaptive immune responses through diverse modalities, aiming to tilt the immune equilibrium toward tumor elimination. Optimal antitumor immunity entails a multifaceted interplay involving NK cells, T cells and DCs, orchestrating immune effector functions. Although DC-based vaccines and NK cells' cytotoxic capabilities hold substantial therapeutic potential, their interaction is frequently hindered by immunosuppressive elements such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells. Chemokines and cytokines, such as CXCL12, CCL2, interferons, and interleukins, play crucial roles in modulating NK/DC interactions and enhancing immune responses. This review elucidates the mechanisms underlying NK/DC interaction, emphasizing their pivotal roles in augmenting antitumor immune responses and the impediments posed by tumor-induced immunosuppression. Furthermore, it explores the therapeutic prospects of restoring NK/DC crosstalk, highlighting the significance of molecules like Sema3E/PlexinD1 in this context, offering potential avenues for enhancing the effectiveness of current immunotherapeutic strategies and advancing cancer treatment paradigms. Harnessing the dynamic interplay between NK and DC cells, including the modulation of Sema3E/PlexinD1 signaling, holds promise for developing more potent therapies that harness the immune system's full potential in combating cancer.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132615","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":"The dysregulation of mitochondrial homeostasis-related genes could be involved in the decrease of mtDNA copy number in systemic lupus erythematosus patients.","authors":"Giada De Benedittis, Andrea Latini, Chiara Morgante, Carlo Perricone, Fulvia Ceccarelli, Giuseppe Novelli, Lucia Novelli, Cinzia Ciccacci, Paola Borgiani","doi":"10.1007/s12026-024-09535-z","DOIUrl":"https://doi.org/10.1007/s12026-024-09535-z","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic multifactorial autoimmune disease. It is now widely demonstrated that oxidative stress (OS) plays an important role in the modulation of the pathogenesis of this disease. Mitochondrial DNA (mtDNA) is highly vulnerable to OS and it is known a decrease of mtDNA copy number in SLE patients. However, to date, it has not been investigated if this decrease is associated with a dysregulation of mitochondrial homeostasis genes. Our aim is to evaluate the amount of mtDNA copy number and the expression of the genes more involved in the mitochondrial homeostasis pathways, in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. We analysed the amount of mtDNA in PBMCs of 72 SLE patients and 61 healthy controls by qPCR. Then, we investigated the expression variability of TFAM and SIRT1 (biogenesis), MFN1 and MFF (fusion/fission) and PRKN2 (mitophagy) genes in a subgroup of SLE patients and healthy controls. Interestingly, we have observed a highly significant decrease in mtDNA copies in SLE patients compared to healthy controls (P < 0.0001). In addition, we have shown that the expression levels of SIRT1, MFN1 and PRKN2 genes were significantly decreased in SLE patients with respect to healthy controls (P = 0.00001 for SIRT1, P = 0.0150 for MFN1 and P = 0.0009 for PRKN2). Lastly, we have reported a positive correlation between PRKN2 expression level and mtDNA copy number (P = 0.019, r = 0.475). In conclusion, our data confirm the impairment of mtDNA copy number in the disease and show for the first time a dysregulation of the mitochondrial homeostasis genes. These results could provide additional support to the important role of mitochondria in SLE development.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125629","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":"Amphotericin B for injection triggers degranulation of human LAD2 mast cells by MRGPRX2 and pseudo-allergic reactions in mice via MRGPRB2 activation.","authors":"Xu He, Xinxin Yang, Longyu Qin, Qianqian Zhang, Xiaolan Ji, Wenjuan Tang, Yingzhuan Zhan, Yanmin Zhang","doi":"10.1007/s12026-024-09532-2","DOIUrl":"https://doi.org/10.1007/s12026-024-09532-2","url":null,"abstract":"<p><p>Amphotericin B, a polyene macrolide antifungal agent, still plays an important role in the management of serious systemic fungal infections. Amphotericin B deoxycholate (AmBd) has been used to treat invasive fungal infections for over 60 years and remains the primary clinical formulation currently available. Anaphylactoid reactions triggered by AmBd in the clinic have been documented. However, the molecular and cellular events contributing to these reactions have not been clearly elucidated to date. This study demonstrates that the human Mas-related G protein-coupled receptor X2 (MRGPRX2) is the receptor that mediates these anaphylactoid responses. Molecular docking and cellular thermal shift assay (CETSA) indicate that AmBd exhibits potential affinity with MRGPRX2. In vitro, exposure to AmBd results in significant release of LAD2 mast cell granules and induces intracellular Ca²⁺ mobilization as well as activation of PLC-γ/IP3R and PI3K/AKT signaling pathways. However, these phenomena are reduced in MRGPRX2-knockdown LAD2 cells. In vivo, AmBd triggers paw swelling and a rapid drop in core body temperature in wild-type (WT) mice. However, these reactions are almost absent in MRGPRB2 (the mouse homolog of MRGPRX2) knockout mice (MRGPRB2^MUT, MUT). The above results suggest that AmBd activates PLC-γ/IP3R and PI3K/AKT signaling via MRGPRX2 (in human LAD2 mast cells) or MRGPRB2 (in mice), leading to the release of mast cell granules and subsequent triggering of pseudo-allergic reactions. Taken together, this study clarifies the role of MRGPRX2 in triggering pseudo-allergic reactions to AmBd and suggests that MRGPRX2 could be a potential therapeutic target for controlling these reactions.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119712","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":"MYOCD and SRF-mediated MLCK transcription prevents polymorphonuclear neutrophils from ferroptosis in sepsis-related acute lung injury.","authors":"Danfeng Pan, Qiu Wu, Chunfeng Zhang, Tao Qin, Tian Jiang, Ximei Wu, Fugen Wu","doi":"10.1007/s12026-024-09529-x","DOIUrl":"https://doi.org/10.1007/s12026-024-09529-x","url":null,"abstract":"<p><p>Persistent activation of polymorphonuclear neutrophils (PMNs) plays a crucial role in the development of sepsis-related acute lung injury (ALI). This study investigated key molecular mechanisms involved in the hyperactivation of PMNs during ALI. A mouse model of sepsis-related ALI was generated by lipopolysaccharide (LPS) injection. RNA sequencing identified myosin light chain kinase (MLCK) as the most significant differentially expressed gene (DEG) between PMNs isolated from model and control mice. Myocardin (MYOCD) and serum response factor (SRF) were two of the DEGs that could promote transcription of MLCK by binding to its promoter. Either knockdown of MLCK, MYOCD, or SRF ameliorated dysfunction and edema in the lungs of LPS-treated mice. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the DEGs are enriched in a ferroptosis-related signaling pathway. The MLCK, MYOCD, or SRF knockdown increased contents of ROS, MDA, ferritin, and ferrous iron, and reduced levels of GSH and GPX4 in the PMNs. However, the MLCK overexpression restored ferroptosis resistance and activity of the PMNs, resulting in increased lung injury. Collectively, this study demonstrates that MYOCD and SRF-mediated MLCK upregulation is correlated with ferroptosis resistance and hyperactivation of PMNs in sepsis-related ALI.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080191","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":"Good syndrome combined with multiple microbial pulmonary infections: case report and review of the literature.","authors":"Yucai Ye, Juan Wang, Bahu Bao, Guorong Chen, Aoyan Hu, Jingzi Sun, Weiying Liu","doi":"10.1007/s12026-024-09528-y","DOIUrl":"https://doi.org/10.1007/s12026-024-09528-y","url":null,"abstract":"<p><p>Good syndrome (GS), a rare acquired immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent infections. This study reports a case of a 37-year-old male GS with multiple pulmonary infections and reviews relevant literature. The patient, with a history of thymoma resection, experienced multiple hospitalizations due to lung infections and neutropenia. The alveolar lavage fluid was detected by macro-genomic sequencing (NGS) to detect multiple pathogens, and targeted anti-infective and immunity-enhancing treatments led to improved symptoms and normal neutrophil counts. A literature review of 98 case reports from 2000 to 2023 was conducted, summarizing the associated diseases and pathogens in GS patients. Regular immunoglobulin monitoring in thymoma patients is essential for early GS diagnosis. When empirical antimicrobial therapy fails, mNGS for pathogen detection and targeted therapy are crucial, and regular IVIG injections can reduce infection rates in GS patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046625","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":"EBV + B cell-derived exosomes promote EBV-associated T/NK-cell lymphoproliferative disease immune evasion by STAT3/IL-10/PD-L1 pathway.","authors":"Wei Chen, Yao Xie, Fan Li, Pengfei Wen, Lin Wang","doi":"10.1007/s12026-024-09531-3","DOIUrl":"https://doi.org/10.1007/s12026-024-09531-3","url":null,"abstract":"<p><p>EBV-associated T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) are characterized by the clonal proliferation of EBV-positive ( +) T/NK cells. EBV is typically latent in B cells and the mechanism by which the EBV genome invades T/NK cells remains unknown. Recent studies have demonstrated that exosomes derived from EBV + B cells play a pivotal role in immunosuppressive microenvironment remodeling. Moreover, the existence of an immunosuppressive microenvironment is known to be critical in the development of EBV-T/NK-LPDs. Hence, we hypothesized that exosomes derived from EBV + B cells might promote the development of EBV-T/NK-LPDs by stimulating immune evasion. In this study, we utilized paraffin sections to clarify the STAT3/IL-10/PD-L1-associated immunosuppressive microenvironment in EBV-T/NK-LPDs. Further, we extracted exosomes from BL2009 (EBV + B cell lymphoma) and CA46 (EBV- B cell lymphoma) cell lines to co-culture with cutaneous T-cell lymphoma (CTCL) cell lines, to verify the changes in the above immune evasion pathway. The paraffin sections of EBV-T/NK-LPDs showed high-expression levels of IL-10/PD-L1, which might be related to the phosphorylation of STAT3. Exosomes derived from EBV + B cells could significantly activate the STAT3/IL-10/PD-L1 pathway. After being treated with C188-9, EBV + B cell-derived exosomes were no longer able to stimulate the expression of IL-10/PD-L1 in CTCL cells. EBV-T/NK-LPDs have a STAT3/IL-10/PD-L1 overactivation-associated immunosuppressive microenvironment. Our study elucidated part of this mechanism. Exosomes derived from EBV + B could induce phosphorylation of STAT3 in CTCL cells, leading to the overexpression of IL-10/PD-L1. Our findings might shed light on new directions for understanding immune evasion in EBV-T/NK-LPDs.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008757","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}