Transplant immunology最新文献

{"title":"Efficacy of waitlist desensitization for lung candidates is limited by antibody rebound","authors":"David Pinelli ,&nbsp;Jennifer Wright ,&nbsp;Amanda Kamar ,&nbsp;Ambalavanan Arunachalam ,&nbsp;Mrinalini Venkata Subramani ,&nbsp;Chitaru Kurihara ,&nbsp;Ankit Bharat ,&nbsp;Catherine Myers","doi":"10.1016/j.trim.2025.102261","DOIUrl":"10.1016/j.trim.2025.102261","url":null,"abstract":"<div><div>HLA antibodies remain a barrier to lung transplantation due to the risk of antibody-mediated rejection (AMR). Desensitization is an option to lower antibody levels and increase access to transplant by reducing risk of AMR. However, concerns remain regarding the efficacy, durability, and risks of administering this treatment while waiting for deceased donor offers. We performed longitudinal antibody assessments for 15 highly sensitized lung candidates undergoing desensitization with plasmapheresis-based treatment protocols. Of the 14 patients transplanted, a significant decrease in overall antibody level was observed in the 2 of 4 patients transplanted within 15 days of the end of their first treatment. Conversely, of the 10 who were transplanted more than 15 days after first treatment, 7 patients rebounded to pre-treatment levels or higher within 3–4 weeks. For the 3 patients in this group who showed a durable decrease, this effect did not manifest until months following treatment. When comparing outcomes for the desensitization cohort against a control group that received treatment post-transplant, no significant differences in survival or acute rejection were observed. These results demonstrate that while plasmapheresis-based waitlist desensitization can effectively remove or reduce the level of HLA antibodies, rebound limits its effectiveness for most patients. To promote successful outcomes, pre-transplant therapy should be targeted to candidates with high lung composite allocation scores likely to be transplanted within the first week after treatment, while aggressive post-transplant immunosuppression may be a safer approach for most highly sensitized patients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102261"},"PeriodicalIF":1.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295014","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":"Identification of genes associated with liver ischemia-reperfusion injury after liver transplantation by WGCNA and PPI network analyses","authors":"Li Jin ,&nbsp;Zhuo Cheng ,&nbsp;Bo Yuan ,&nbsp;Siming Qu ,&nbsp;Jie Lin ,&nbsp;Lin Deng ,&nbsp;Benkai Wei ,&nbsp;Hangpin Wang ,&nbsp;Youzhi Ye ,&nbsp;Zhong Zeng ,&nbsp;Hanfei Huang","doi":"10.1016/j.trim.2025.102249","DOIUrl":"10.1016/j.trim.2025.102249","url":null,"abstract":"<div><div>Liver transplantation is the only effective treatment for end-stage liver disease. The success of transplantation largely relies on liver ischemia/reperfusion injury (LIRI). However, the pathogenesis of LIRI remains unclear. In this study, we used the public dataset GSE12720, which contains liver transplants from both living and deceased donors, to identify differentially expressed genes (DEGs) before and after reperfusion. Weighted gene co-expression network analysis (WGCNA) was used to identify related genes. A protein–protein interaction network containing 85 overlapping DEGs and WGCNA genes was constructed. Using Molecular Complex Detection and cytoHubba plug-ins in Cytoscape and Kyoto Encyclopedia of Genes and Genomes analyses, we identified 5 core pathways and 13 hub genes (<em>IL-1β, JUN, TNFAIP3, CCL2, ICAM1, CCL20, SOCS3, IRF1, BIRC3, GADD45B, MYC, CCL4, and BCL2A1</em>). These findings were validated using two independent datasets (GSE14951 and GSE15480) and a mouse LIRI model, which effectively confirmed the expression levels of 13 hub genes. This study aimed to use advanced bioinformatics methods to investigate hub genes related to LIRI to identify new biomarkers and improve our understanding of LIRI pathogenesis.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102249"},"PeriodicalIF":1.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286589","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":"Comparative efficacy of Naringenin and Sinomenine in facilitating the differentiation of mouse hematopoietic stem cells into immature dendritic cells to promote transplantation immunological regulation","authors":"Cuixiang Xu ,&nbsp;Xiangrong Zhao ,&nbsp;Zejiaxin Niu ,&nbsp;Ying Wang ,&nbsp;Xinlu Jiang ,&nbsp;Jiaxin Tian ,&nbsp;Yangmeng Feng ,&nbsp;Xiaoyan Huang ,&nbsp;Puxun Tian","doi":"10.1016/j.trim.2025.102260","DOIUrl":"10.1016/j.trim.2025.102260","url":null,"abstract":"<div><h3>Objective</h3><div>Immature dendritic cells (imDC) are crucial in facilitating transplant immunological regulation. However, imDC is readily amenable to maturation. Sinomenine (Sin) naringin (Nar) are traditional Chinese medicine with immunoregulation and anti-inflammatory activities. We investigated the effect of Sin and Nar on the generation of immature dendritic cells (imDC) and their ability to prolong the survival of skin allografts in mice.</div></div><div><h3>Methods</h3><div>Hematopoietic stem cells (HSC) obtained from bone marrow prompted to develop into immature dendritic cells (imDC) through treatment with Sin (Sin-HSC-imDC) or Nar (Nar-HSC-imDC). The cell counting kit-8 (CCK-8) assay was employed to assess the differentiating efficacy of Sin-HSC-imDC and Nar-HSC-imDC. DC surface markers and apoptosis following lipopolysaccharide (LPS) treatment were assessed by flow cytometry, while apoptosis-related genes using qPCR. The impact of Sin-HSC-imDC and Nar-HSC-imDC on the generation of regulatory T cells (Tregs) was evaluated by mixed lymphocyte reactions. Cytokine expression was quantified using enzyme-linked immunoassays (ELISA). The immunomodulatory effects of Sin-HSC-imDC and Nar-HSC-imDC were evaluated by performing skin transplantation experiments in Balb/c mice recipients models. Kaplan-Meier technique was employed for graft survival outcomes.</div></div><div><h3>Results</h3><div>In vitro assays, in comparison to Sin-HSC-imDC, Nar-HSC-imDC had higher CD11c expression and lower CD80 as markers for imDCs (<em>P</em> <em>&lt;</em> <em>0.05</em>) and promoted the generation of Tregs proliferation (<em>P</em> <em>&lt;</em> <em>0.05</em>). Interleukin 2 (IL-2) and interferon gamma (IFN-γ) levels diminished in Nar-HSC-imDC groups (<em>P</em> <em>&lt;</em> <em>0.05</em>), but interleukin 10 (IL-10) and transforming growth factor-beta (TGF-β) levels elevated (<em>P</em> <em>&lt;</em> <em>0.05</em>). And the apoptosis rate of Nar-HSC-DC increased significantly after LPS treatment (<em>P</em> <em>&lt;</em> <em>0.05</em>). In vivo assays, when Balb/c mice received Nar-HSC-imDC or Sin-HSC-imDC via the tail vein seven days before skin transplantation, mice from the Nar-HSC-imDC group had increased CD4⁺CD25⁺CD127⁻ Tregs proliferation in the spleen (<em>P</em> <em>&lt;</em> <em>0.05</em>), which prolonged skin graft survival, and that was better than in Sin-HSC-imDC group.</div></div><div><h3>Conclusion</h3><div>Nar was exposured more efficient in inducing differentiation of HSC into imDC than Sin. Nar-HSC-imDC had stronger ability in inducing specific immune hypo-responsiveness than Sin-HSC-imDC.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102260"},"PeriodicalIF":1.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262741","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 PD-L1 and CTLA-4 levels as biomarkers of acute rejection and renal dysfunction in kidney transplant recipients","authors":"Angelica Canossi ,&nbsp;Fabio Vistoli ,&nbsp;Pierluigi Sebastiani ,&nbsp;Alessia Colanardi ,&nbsp;Tiziana Del Beato ,&nbsp;Alessandra Panarese","doi":"10.1016/j.trim.2025.102250","DOIUrl":"10.1016/j.trim.2025.102250","url":null,"abstract":"<div><h3>Purpose</h3><div>Acute rejection in kidney transplantation is a critical barrier to long-term graft survival and the PD-1/PD-L1 and CTLA-4 molecules are crucial for the tolerance of alloreactive T cells against tubular epithelial cells. Our study aims to assess the role of these soluble PD-L1 and CTLA-4 molecules as biomarkers for <em>non-invasive</em> immunosurveillance after renal transplantation.</div></div><div><h3>Methods</h3><div>Blood samples from 65 recipients were investigated for serum sPD-L1 and sCTLA-4 molecules at the time of kidney transplantation (baseline), in 3 time-points (15, 60 and 365 days) post-transplant, and when acute rejection (ACR) was suspected. Samples and standards were processed in duplicate using sandwich ELISA.</div></div><div><h3>Results</h3><div>We revealed dynamic changes in serum expression over time, with a significant decrease from the time of kidney transplantation to the various monitoring points, except at the time of acute rejection when the levels increased. Multivariable logistic regression revealed that the sPD-L1 15-day post-transplant is an independent variable for ACR onset (AOR = 1.196 <em>p</em> = 0.020), and with a moderate discriminatory power (AUC = 0.717, <em>p</em> = 0.031), together with PD-L1 60 days, for the occurrence of rejection within 1 year from transplant. sPD-L1 after 15 days shows a predictive role also for DGF (AUC = 0.738, <em>p</em> = 0.001) and graft dysfunction at 60 days (AUC = 0.672, <em>p</em> = 0.022). Furthermore, a higher 15-day expression of sCTLA-4 in patients with ACR compared with those with stable graft (114.8 pg/mL vs. 67.8 pg/mL, <em>p</em> = 0.018) was reported.</div></div><div><h3>Conclusion</h3><div>These analyses suggest the potential role of these serum molecules as dynamic biomarkers of inflammation and immunoregulation in AKI and acute rejection; they may indicate new immunotherapy targets, useful for modulating tolerance and assist the clinician in identifying patients at risk of rejection or kidney failure.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102250"},"PeriodicalIF":1.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240887","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":"Identification of allogeneic and xenogeneic neural stem cells' immunogenicity in the brain and strategies to alleviate transplantation rejection","authors":"Xiangyu Ma ,&nbsp;Ho Jin Lee ,&nbsp;Dong Oh. Kim ,&nbsp;Young Do Kwon ,&nbsp;Geun-Hyoung Ha ,&nbsp;Chung Kwon Kim ,&nbsp;Hyun Nam ,&nbsp;Je Young Yeon ,&nbsp;Kyunghoon Lee ,&nbsp;Sun-Ho Lee ,&nbsp;Kyeung Min Joo","doi":"10.1016/j.trim.2025.102247","DOIUrl":"10.1016/j.trim.2025.102247","url":null,"abstract":"<div><div>Neural stem cells (NSCs) are a promising therapy for central nervous system (CNS) disorders, yet post-transplant immune rejection critically compromises their survival and efficacy. In this study, we demonstrated the neuroinflammatory responses triggered by syngeneic, allogeneic, and xenogeneic NSCs transplantation, and evaluated the immunosuppressive effects of cyclosporine A (CyA) and methylprednisolone (MP) on graft rejection. Our findings revealed that xenogeneic NSCs transplantation induced infiltration of neutrophils (<em>p</em> &lt; 0.0001<strong>)</strong>, microglia/macrophages (<em>p</em> &lt; 0.0001<strong>)</strong>, CD4⁺ and CD8⁺ T cells (<em>p</em> &lt; 0.0001<strong>)</strong>, while allogeneic transplantation primarily triggered microglia/macrophages (<em>p</em> &lt; 0.0005) recruitment. Both transplantation types caused a sharp decline in grafted cell numbers (<em>p</em> &lt; 0.005). Combinatorial CyA and MP treatment significantly attenuated xenogeneic immune rejection and markedly increased surviving graft cells in the brain. Similarly, MP monotherapy effectively reduced allogeneic rejection and enhanced transplanted cell survival. Overall, allogeneic NSCs transplantation primarily triggers innate immunity, while xenogeneic transplantation causes both innate and adaptive immune responses. Accordingly, xenogeneic transplantation required combined CyA and MP therapy, whereas MP monotherapy mitigated rejection in allogeneic transplantation. Our findings may offer a strategy to mitigate transplantation rejection of allogeneic and xenogeneic NSCs in the brain, thereby optimizing the microenvironment for NSC-based therapies in preclinical and clinical applications for various CNS disorders.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102247"},"PeriodicalIF":1.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222642","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":"Immunosuppression minimization and withdrawal in liver transplantation: The “holy grail”?","authors":"V.U. Lakshmi ,&nbsp;Mohammed Riyas ,&nbsp;Dinesh Balakrishnan ,&nbsp;M.P. Narmadha ,&nbsp;S. Sudhindran","doi":"10.1016/j.trim.2025.102248","DOIUrl":"10.1016/j.trim.2025.102248","url":null,"abstract":"<div><div>Liver transplantation typically necessitates the use of life long immunosuppressive drugs, to suppress the immune system and minimize the risk of rejection. Prolonged use of immunosuppressive drugs can, however, lead to various side effects, including an increased risk of infections, renal dysfunction, and several metabolic complications. To address this, transplant professionals work to tailor immunosuppression to the patient needs, with the ultimate goal of minimizing drug doses.The “holy grail” of immunosuppression following liver transplantation has been its complete withdrawal. Over the past decade, researchers have juggled with immunosuppression minimization in recipients of liver grafts, but the results were disparate due to the diversity in study designs and limited sample size. Nevertheless, immunosuppression withdrawal has been observed possible in approximately 20 % of strictly selected recipients, particularly in extremes of age and when performed over a prolonged period. The predominant stumbling-block was the occurrence of rejection during the process of immunosuppression withdrawal. Currently, there is a lack of scientific evidence for selecting patients in whom immunosuppressant minimization would be possible without risk of allograft rejection and on the precise methods of immunosuppression withdrawal.The development of clinical tools for personalized medication adjustments and a broader comprehension of the pathogenesis of late graft rejection are essential for this. This article centers on the physiological mechanisms of immune tolerance, strategies for minimizing and withdrawing immunosuppression after liver transplantation, and the biomarkers indicative of sustained tolerance in liver transplantation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102248"},"PeriodicalIF":1.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226842","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":"Recombinant human thrombopoietin reduces the risk of acute graft-versus-host-disease and its mechanism","authors":"Hairong Fei ,&nbsp;Xiaodan Liu ,&nbsp;Xiaolin Ma ,&nbsp;Feng Hou ,&nbsp;Peng Jiang ,&nbsp;Lingjie Sun ,&nbsp;Shanshan Liu ,&nbsp;Tianlan Li ,&nbsp;Chunting Zhao","doi":"10.1016/j.trim.2025.102246","DOIUrl":"10.1016/j.trim.2025.102246","url":null,"abstract":"<div><h3>Objective</h3><div>Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of recombinant human thrombopoietin (rhTPO) on aGVHD using retrospective clinical data and a xenogeneic GVHD mouse model.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 162 patients who underwent allo-HSCT between 2016 and 2018, comparing outcomes between those treated with rhTPO and those who were not. Additionally, a murine GVHD model was established using irradiated Balb/c mice that received allogeneic PBMCs. Mice were treated with different doses of rhTPO to assess organ pathology, immune cell subsets, and cytokine expression. PBMCs from humans were also treated with rhTPO to assess proliferation and differentiation in vitro. Results were presented as odds ratios (OR) with 95 % confidence intervals (CI), and statistical significance was set at <em>P</em> &lt; 0.05. <em>P</em> &gt; 0.05 was considered statistically significant. All experiments were repeated for 3 times.</div></div><div><h3>Results</h3><div>Clinical analysis showed that rhTPO use and older patient age were independently associated with a lower incidence of aGVHD (<em>P</em> = 0.007 and <em>P</em> = 0.014, respectively). In the xenogeneic mouse model, rhTPO mitigated tissue pathology and modulated immune cell subsets. In vitro, rhTPO regulated PBMC proliferation and enhanced lymphocyte differentiation.</div></div><div><h3>Conclusions</h3><div>rhTPO may reduce the risk of aGVHD by modulating immune responses and protecting tissues, supporting its potential role as an adjunct therapy in allo-HSCT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102246"},"PeriodicalIF":1.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209629","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":"Early post-lung transplant cell-free DNA levels are associated with baseline lung allograft function","authors":"Andrea Zajacova ,&nbsp;Majd Alkhouri ,&nbsp;Goncalo Ferrao ,&nbsp;Miray Guney ,&nbsp;David Rezac ,&nbsp;Kristyna Vyskocilova ,&nbsp;Tereza Kotowski ,&nbsp;Alzbeta Dutkova ,&nbsp;Eliska Dvorackova ,&nbsp;Robert Lischke ,&nbsp;Libor Fila ,&nbsp;David J. Ross ,&nbsp;Bart Vanaudenaerde ,&nbsp;Jan Havlin","doi":"10.1016/j.trim.2025.102245","DOIUrl":"10.1016/j.trim.2025.102245","url":null,"abstract":"<div><h3>Background</h3><div>Baseline lung allograft dysfunction (BLAD) is defined as the failure to achieve normal pulmonary function—specifically, forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) values of ≥80 %—within the first year after lung transplantation. It is hypothesised that early subclinical injury, reflected by elevated donor-derived cell-free DNA (dd-cfDNA), both in absolute concentration and percentage (dd-cfDNA%), as well as total cell-free DNA (cfDNA), may be predictive of subsequent BLAD development.</div></div><div><h3>Methods</h3><div>We included patients who underwent bilateral lung transplantation between May 2021 and September 2023. Blood samples collected between 3 and 9 months post-transplantation were analysed for dd-cfDNA%, dd-cfDNA concentration (copies/mL), and estimated total cfDNA (copies/mL). BLAD was defined by failure to achieve both FEV₁ and FVC ≥80 % of predicted values within the first year.</div></div><div><h3>Results</h3><div>A total of 158 samples from 37 patients were analysed. Ten patients (27 %) met the BLAD criteria. Those with BLAD had significantly higher dd-cfDNA levels (median: 39 cp/mL) compared to non-BLAD patients (26 cp/mL; <em>p</em> = 0.01). Similarly, total cfDNA levels were significantly elevated in the BLAD group (22,809 cp/mL vs. 13,840 cp/mL; <em>p</em> = 0.002). However, dd-cfDNA% did not differ significantly (0.23 % vs. 0.15 %; <em>p</em> = 0.2).</div></div><div><h3>Conclusion</h3><div>Elevated absolute dd-cfDNA and total cfDNA levels in the early post-transplant period were associated with BLAD, suggesting that cfDNA may serve as a potential predictive biomarker. These findings support the potential of cfDNA-based biomarkers to enhance early detection of graft dysfunction, warranting validation in larger cohorts.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102245"},"PeriodicalIF":1.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209628","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":"Rapamycin-modified CD169low/-tolDC promotes skin graft survival in mice via IL-10+Breg","authors":"Xi Lu ,&nbsp;Yu-di Han ,&nbsp;Xiao-ran Zu ,&nbsp;Jin-can Huang ,&nbsp;Li Li ,&nbsp;Meng Wang ,&nbsp;Yu-Ting Wang ,&nbsp;Ling-li Guo ,&nbsp;Lin Zhou ,&nbsp;Yan Han","doi":"10.1016/j.trim.2025.102244","DOIUrl":"10.1016/j.trim.2025.102244","url":null,"abstract":"<div><div>Skin allografts are prone to rejection because of their high immunogenicity. By achieving immune tolerance, the long-term survival of skin allografts can be extended without the need for immunosuppressants or with only short-term low-dose dependency. Tolerogenic dendritic cells (tolDCs) show a strong potential for graft tolerance. We explored the mechanism whereby rapamycin-modified CD169low/-tolDCs regulate interleukin-10 (IL-10) B regulatory (IL-10+ Breg) cell production and mediate the long-term survival of skin allografts in mice. CD169low/-tolDCs were obtained through flow cytometry sorting after treating the mesenchymal stem cell (MSC)-derived dendritic cells with a low dose of GM-CSF. A treatment regimen combining preoperative stimulation and postoperative adoptive infusion of CD169low/-tolDCs was used to treat an acute rejection (AR) mouse skin transplantation model—the adoptive infusion group. An equivalent dose of saline was administered to the control group. Survival and graft rejection rates were assessed. Mixed lymphocyte culture, flow cytometry, immunohistochemistry (IHC), and western blotting (WB) were used to elucidate the expression of different IL-10+ Breg subsets in mice treated with adoptive infusion therapy and the molecular mechanisms whereby CD169low/-tolDCs induce IL-10+ Breg production to mediate tolerance. Adoptive infusion of CD169low/−tol DCs markedly prolonged the rejection time after skin transplantation in mice and promoted graft survival. A significant increase was observed in local blood flow signals in the transplanted skin, along with mild local inflammation. Flow cytometric analysis revealed a positive correlation between high expression of IL-10+ Breg and the changes in Foxp3+ Tregs in vivo, primarily enriched in the CD19 + CD24 + CD27+ mBreg and CD19 + CD23 + CD27-CD24+ Breg subsets, with higher levels of IgM expression. Significant differences were observed compared with control mice. CD79b/NF-κB pathway was found to be involved in Breg production. CD24, CD23, CD79, BTK, NF-κB p50/p65, CD40, and IKKα levels in the adoptive infusion group were significantly increased compared with those in the control group. Adoptive infusion of CD169low/-MSCs/tolDCs may activate the NF-κB pathway through CD79/BTK-dependent and CD40/IKKα-independent pathways, inducing high expression of IL-10 + Breg and promoting graft survival of mouse skin transplantation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102244"},"PeriodicalIF":1.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143617","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":"Successful use of cemiplimab in a high immunologic risk kidney transplant recipient with metastatic squamous cell carcinoma","authors":"Elena-Bianca Barbir ,&nbsp;Abdullah Jalal ,&nbsp;Joseph Grande ,&nbsp;Svetomir N. Markovic ,&nbsp;Aleksandra Kukla ,&nbsp;Itunu Owoyemi","doi":"10.1016/j.trim.2025.102242","DOIUrl":"10.1016/j.trim.2025.102242","url":null,"abstract":"<div><div>The widespread use of immunotherapy in the management of cancers has led to improved overall survival and progression free survival. Due to increased risk of allograft rejection, organ transplant recipients are often excluded in clinical trials or offered immunotherapy only as salvage therapy. We report a case of successful use of Cemiplimab, an immune checkpoint inhibitor, in a high immunologic risk kidney transplant recipient who was diagnosed with metastatic squamous cell carcinoma (SCC) twenty-five months post-transplant. He started Cemiplimab five months post diagnosis of SCC, as third line therapy, after demonstrating progression of metastatic skull-based disease on prior lines of therapy. His maintenance immunosuppression was changed from triple immunosuppression with tacrolimus, mycophenolate and prednisone to sirolimus with a high trough target of 10–15 ng/mL and steroid therapy. He tolerated the high sirolimus trough and continued on Cemiplimab for six months with clinically stable allograft function and a good quality of life. Notably, he demonstrated response of his previously chemotherapy refractory metastatic disease. He passed away from radiation necrosis of the brain at sixty-eight months post-transplant.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102242"},"PeriodicalIF":1.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143624","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}