Human Immunology最新文献

{"title":"HLA DRB1*01:02 allele is associated with anti-AT1R antibodies production in kidney transplanted patients.","authors":"Ilaria Carelli, Alessandro Romano, Angelo Corso Faini, Cristiana Caorsi, Gabriele Maria Togliatto, Claudia Maria Rosso, Gina Mazzola, Elena Garino, Silvia Alizzi, Paola Magistroni, Luigi Biancone, Vincenzo Cantaluppi, Tiziana Vaisitti, Silvia Deaglio, Antonio Amoroso","doi":"10.1016/j.humimm.2026.111745","DOIUrl":"https://doi.org/10.1016/j.humimm.2026.111745","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation is lifesaving treatment for end-stage renal disease, yet immune-mediated complications limit long-term graft survival. Non-HLA antibodies (NHLA), particularly anti-Angiotensin type 1 receptor antibodies (AT1R-abs), are emerging mediators of graft injury. This study investigated whether selective HLA alleles influence AT1R-ab development in kidney transplant recipients.</p><p><strong>Material and methods: </strong>We analyzed a cohort of 59 kidney recipients carrying the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype and 52 controls. Pre- and post-transplant sera were tested for donor-specific anti-HLA antibodies via Luminex-based single antigen bead assay and AT1R-ab via enzyme-linked immunosorbent assay and categorized as positive (≥17 U/mL), intermediate (10.1-16.9 U/mL) and negative (≤10 U/mL). In silico analysis were performed to assess peptide binding to HLA haplotypes.</p><p><strong>Results: </strong>AT1R-abs were markedly enriched in the DR1 patients, both pre- (p = 0.0009) and post-transplant (p < 0.0001), at variance with controls, who were rarely positive. In silico prediction revealed that HLA-DRB1*01:02, typically the involved DRB1*01 subtype of the above-mentioned haplotype, can present AT1R peptides with greater binding affinity.</p><p><strong>Conclusions: </strong>These results suggest a possible genetic link between HLA haplotypes and AT1R-ab development in kidney transplant recipients, probably due to a higher binding affinity of some AT1R-derived peptides to HLA-DRB1*01:02. Understanding this association may enable personalized immunosuppressive therapies.</p>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":" ","pages":"111745"},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823677","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":"A wide proteome analysis to engineer an efficient epitope based vaccine against Salmonella Typhi: An immunoinformatic study","authors":"Mahsa Beiranvand ,&nbsp;Nemat Shams ,&nbsp;Amin Jaydari ,&nbsp;Narges Nazifi ,&nbsp;Peyman Khademi","doi":"10.1016/j.humimm.2026.111684","DOIUrl":"10.1016/j.humimm.2026.111684","url":null,"abstract":"<div><h3>Background</h3><div>Typhoid fever, a potentially fatal disease caused by <em>Salmonella</em> enterica serovar Typhi, requires effective vaccines. This study aimed to design a recombinant subunit vaccine using the most immunogenic proteins from the <em>Salmonella</em> Typhi proteome.</div></div><div><h3>Methods</h3><div>Initially, the most antigenic proteins were selected to predict linear T-cell, B-cell, and IFN-γ epitopes. A recombinant construct incorporating these epitopes, peptide linkers, and a molecular adjuvant was designed. Comprehensive evaluation assessed physicochemical properties, solubility, secondary/tertiary structure, antigenicity, and immune stimulation potential. Molecular docking and dynamics simulations investigated binding to the TLR4/MD2 receptor complex.</div></div><div><h3>Results</h3><div>Seven proteins from 4322 were chosen for epitope prediction, yielding a 655-amino acid construct. Physicochemical analysis showed 40.31 % hydrophobic amino acids, an aliphatic index of 53.66, GRAVY index of −0.712, and instability index of 22.34. Structural composition was 53.53 % alpha-helix, 8.85 % extended strand, and 40.61 % random coil. Immune simulations demonstrated significant enhancement of primary/secondary humoral and cellular immune responses. The vaccine construct effectively bound the TLR4/MD2 receptor via significant hydrogen bonding (affinity: −1019.1 kcal/mol). Molecular dynamics simulations confirmed the stability of this interaction over 200 ns, demonstrating that both the vaccine candidate and receptor remained structurally stable throughout the simulation period.</div></div><div><h3>Conclusion</h3><div>Typhoid vaccine candidate shows immunogenic properties, robust immune responses and stable TLR4/MD2 receptor binding.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111684"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183455","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 role of complement protein and complement regulatory protein in diabetic nephropathy","authors":"Xiaoxiang Jiang ,&nbsp;Zhanzhan Sun","doi":"10.1016/j.humimm.2026.111686","DOIUrl":"10.1016/j.humimm.2026.111686","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy is one of the main causes of end-stage renal disease, with dysregulation of the complement system playing a critical role in its pathogenesis. However, the specific mechanisms, key effector molecules, and relevant therapeutic targets still require further investigation.</div></div><div><h3>Methods</h3><div>This review involves searching databases such as PubMed and Web of Science to identify and integrate key studies on the role of complement proteins and regulatory proteins in diabetic nephropathy. This is a narrative review integrating experimental and clinical studies, rather than a formal systematic review. The analysis systematically examines the mechanisms of the complement system in disease progression and its potential as a therapeutic target.</div></div><div><h3>Results</h3><div>This review collectively suggests that the hyperglycemic environment characteristic of diabetic nephropathy activates both the complement alternative and lectin pathways, continuously driving the complement cascade and generating key effector molecules (such as C5a and the membrane attack complex). These molecules directly lead to podocyte injury, glomerular inflammation, and fibrosis. Concurrently, dysfunction of complement regulatory proteins (such as CD59 and CD55) results in excessive activation of complement proteins, collectively accelerating the progression of diabetic nephropathy to end-stage renal disease. In terms of intervention strategies, inhibitors targeting specific complement components (such as C3 and C5) have shown protective effects in preclinical models.</div></div><div><h3>Conclusion</h3><div>Dysregulation of the complement system is an important pathogenic mechanism in diabetic nephropathy. A deeper understanding of this regulatory network provides a solid theoretical foundation for developing targeted and precise therapeutic strategies aimed at the complement system.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111686"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192375","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":"Prevalence and dynamics of HLA Donor-Specific antibodies in Simultaneous Liver-Kidney transplantation","authors":"Qiuheng Zhang ,&nbsp;Mario A. Pulido ,&nbsp;Sofia Soltero ,&nbsp;Carrie Butler ,&nbsp;Erik Lum ,&nbsp;Basmah Abdalla ,&nbsp;Elizabeth Kendrick ,&nbsp;Julie M. Yabu ,&nbsp;Phuong-Thu Pham ,&nbsp;Suphamai Bunnapradist ,&nbsp;Jeffrey Veale ,&nbsp;Albin H. Gritsch ,&nbsp;Gabriel M. Danovitch ,&nbsp;Robert S. Venick ,&nbsp;Harry Pickering ,&nbsp;Douglas G. Farmer ,&nbsp;Elaine F. Reed","doi":"10.1016/j.humimm.2026.111679","DOIUrl":"10.1016/j.humimm.2026.111679","url":null,"abstract":"<div><h3>Aims</h3><div>Donor-specific antibodies (DSAs) negatively affect outcomes in solid organ transplantation outcomes, but their significance in simultaneous liver-kidney (SLK) transplant recipients remains incompletely understood. This study investigates the prevalence, dynamics, and clinical impact of both preformed and posttransplant DSAs in patients undergoing SLK transplantation.</div></div><div><h3>Methods</h3><div>A retrospective cohort of 151 SLK recipients transplanted at UCLA from 2014 to 2024 was analyzed. Assessment of DSA status, DSA strength (mean fluorescence intensity (MFI), and clinical outcomes including rejection and patient survival were performed. Patient survival was analyzed using Kaplan–Meier survival curves.</div></div><div><h3>Results</h3><div>Of the 151 patients, 35 (23.2 %) were transplanted with preformed DSAs. Among 110 patients with posttransplant DSA testing, 25 (22.7 %) developed new DSAs, with a significantly higher incidence in females (37.8 % vs. 15.1 %, <em>p</em> = 0.014). Preformed DSAs were not significantly associated with rejection in kidney, liver, or combined allografts. However, posttransplant DSAs correlated with increased rejection risk: 3/25 (12 %) vs. 1/85 (1.2 %) in kidney (<em>p</em> &lt; 0.05) alone and 12 % vs. 8.2 % in liver (<em>p</em> &lt; 0.05) alone. Four patients experienced antibody-mediated rejection, and all four patients had either preformed or posttransplant <em>de novo</em> DSA. Preformed Class II DSAs were more persistent posttransplant and were more frequently associated with rejection (p &lt; 0.05). Both preformed and posttransplant DSAs significantly declined over time posttransplant, although class II DSAs exhibited more resistance to clearance compared to class I DSA. Survival analysis revealed no statistically significant differences among patients without DSA, preformed DSA and posttransplant DSA groups; however, patients without DSAs had the highest 5-year survival (74.3 %), while those developing de novo DSAs beyond 3 months had the lowest (48.4 %).</div></div><div><h3>Conclusions</h3><div>In SLK recipients, posttransplant DSAs, especially class II, are significantly associated with increased rejection risk and may contribute to reduced long-term survival. Although preformed DSAs showed less clinical impact, persistent class II DSAs warrant closer monitoring. Larger studies are needed to validate these findings and guide individualized immunological risk assessment.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111679"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192438","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":"Preclinical and Clinical Developments in Treg Therapy for Heart Transplantation: Critical Assessment and Translational Challenges","authors":"Konstantinos Mengrelis ,&nbsp;Laurenz Wolner ,&nbsp;Rayna Lellis Lakatos ,&nbsp;Andreas Zuckermann ,&nbsp;Nina Pilat","doi":"10.1016/j.humimm.2026.111681","DOIUrl":"10.1016/j.humimm.2026.111681","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) represent a promising approach to induce donor-specific tolerance in cardiac transplantation, potentially reducing reliance on chronic immunosuppression. This review critically evaluates preclinical and clinical evidence. Preclinical studies demonstrate that adoptively transferred Tregs prolong cardiac allograft survival and prevent chronic allograft vasculopathy (CAV) in murine models through multiple suppressive mechanisms. Phase I/II trials in kidney and liver transplantation have already confirmed safety and feasibility of polyclonal Treg cell therapy, with evidence of immunosuppression reduction in selected patients. However, no cardiac-specific trials have been completed in adults, and critical translational barriers persist including limited in vivo persistence, phenotypic instability under inflammatory conditions, manufacturing complexity and incompatibility with deceased donor timelines. Emerging approaches show promise: CAR-engineered Tregs targeting HLA-A2 demonstrate enhanced specificity and establish infectious tolerance in preclinical cardiac transplant models, with preliminary data from the first-in-human kidney transplant data suggesting safety and efficacy. Thymus-derived Tregs offer advantages for pediatric recipients, with the first treated cardiac transplant patient showing preserved Treg homeostasis. This review identifies key research priorities necessary to translate Treg therapy into clinical cardiac transplantation practice.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111681"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167900","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 limited clinical utility of Neutrophil-to-Lymphocyte ratio in systemic lupus Erythematosus: A Meta-Analysis with external validation","authors":"Jingxue Du ,&nbsp;Xiangping Tu ,&nbsp;Manrong He ,&nbsp;Yongdi Zuo,&nbsp;Lei Chen,&nbsp;Mengfei Li,&nbsp;Wanxin Tang","doi":"10.1016/j.humimm.2026.111683","DOIUrl":"10.1016/j.humimm.2026.111683","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the diagnostic and discriminative value of the neutrophil-to-lymphocyte ratio (NLR) in systemic lupus erythematosus (SLE).</div></div><div><h3>Methods</h3><div>A <em>meta</em>-analysis was conducted using literature from inception to January 2026. Pooled estimates were calculated, and external validation was provided by a single-center study (n = 290).</div></div><div><h3>Results</h3><div>Forty studies were included. NLR was significantly higher in SLE patients than healthy controls (SMD = 0.850). Patients with lupus nephritis (LN) and active disease also exhibited elevated NLR. A positive correlation was found between NLR and SLEDAI scores (pooled r = 0.330); however, this decreased to 0.200 after trim-and-fill adjustment for publication bias, a finding consistent with external validation (r = 0.210). Its discriminatory accuracy was generally limited (AUC 0.668–0.757), with ethnicity and treatments being major sources of heterogeneity.</div></div><div><h3>Conclusion</h3><div>NLR is elevated in SLE, LN, and active disease, showing a weak positive correlation with disease activity. However, its clinical utility is influenced by ethnicity and treatment, indicating that it should not be used as an independent biomarker but may have a role as part of a combined assessment.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111683"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116507","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":"Unique case of False-Positive pan-HLA-A antibody detection in LABScreen single antigen bead assay","authors":"Merschman Jarret,&nbsp;Barnes Rachel,&nbsp;Burmeister Lydia,&nbsp;Kreuter Justin,&nbsp;Park Robyn,&nbsp;Theel Nathan,&nbsp;Wakefield Laurie,&nbsp;Manish J. Gandhi","doi":"10.1016/j.humimm.2026.111682","DOIUrl":"10.1016/j.humimm.2026.111682","url":null,"abstract":"<div><div>Accurate detection of HLA antibodies is essential for assessing immunologic risk in transplantation. Solid-phase antibody assays (SPA), particularly Luminex-based single-antigen bead (SAB) assay offer high sensitivity, but are prone to false reactions that may lead to clinical misinterpretation. While false-positive pan-locus patterns have been described for HLA-C/DR, pan-HLA-A reactivity has not been previously reported.</div><div>We present a patient who developed pan-HLA-A reactivity detected by LABScreen™ SAB one year after combined liver-kidney transplantation. Repeat testing and Presorb™ treatment yielded identical results. To investigate causes, testing with acid-treated beads ruled out antibodies to denatured HLA. An alternative SAB platform (LIFECODES® LSA™) and LABScreen™ Mixed beads were negative. Surrogate flow crossmatches with two unrelated donors were negative, confirming absence of cell-reactive antibodies.</div><div>This represents the first documented case of false-positive pan–HLA-A reactivity confined to a single commercial SAB product. Recognition of such artifacts is essential to prevent misclassification of antibody specificity.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111682"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167994","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":"Single-cell transcriptomics reveals targeted modulation of inflammatory repertoire by SOCE blockers","authors":"Andreas Stephanou ,&nbsp;Madhav Mantri ,&nbsp;Divya Shankaranarayanan ,&nbsp;Carol Li ,&nbsp;Mila Lagman ,&nbsp;Jenny Xiang ,&nbsp;Chendong Pan ,&nbsp;Yanjie Sun ,&nbsp;Thangamani Muthukumar ,&nbsp;Khaled Machaca ,&nbsp;Iwijn De Vlaminck ,&nbsp;Manikkam Suthanthiran","doi":"10.1016/j.humimm.2026.111687","DOIUrl":"10.1016/j.humimm.2026.111687","url":null,"abstract":"<div><div>Store-operated calcium entry (SOCE) plays a critical role in regulating intracellular calcium signaling and is essential for immune cell functions. SOCE blockade with the pyrazole derivative BTP2 has been explored as an anti-inflammatory strategy in preclinical models, and Zegocractin (CM4620) is under clinical investigation as a CRAC channel inhibitor with activity in multiple tissues, including immune cells. However, the cell type–specific consequences of SOCE blockade under defined activation contexts remain incompletely understood. Here, we used multiplexed single-cell RNA sequencing to investigate the effects of two prototypic SOCE blockers, BTP2 and CM4620, on polyclonally stimulated, normal human peripheral blood mononuclear cells (PBMCs) in a phytohemagglutinin (PHA)-driven T-cell activation model. The data revealed that SOCE blockade suppressed cytotoxicity-associated transcriptional programs in CD8⁺ effector T cells and natural killer (NK) cells, restoring them to levels comparable to unstimulated cells. At the same time, SOCE blockade allowed CD4⁺ regulatory T cells to retain transcriptional signatures associated with immune regulation. These results indicate that, in this experimental model, SOCE blockade dampens cytotoxic programs while maintaining tolerance signatures, suggesting a potential avenue for targeted immune modulation in transplantation and other immune-mediated conditions.</div></div><div><h3><strong>Significance Statement</strong></h3><div>Store-operated calcium entry (SOCE) is essential for immune activation, but broad immunosuppression can cause significant side effects. Using single-cell transcriptomics in a phytohemagglutinin (PHA)–driven T-cell activation model, we show that SOCE blockade with BTP2 or CM4620 suppresses pro-inflammatory and cytotoxic programs in CD8⁺ effector T cells and NK cells while preserving tolerance-associated pathways in CD4⁺ regulatory T cells. These findings suggest that SOCE blockade may provide a more targeted form of immune modulation, warranting future head-to-head comparisons with conventional immunosuppressants. Our results highlight the potential of SOCE blockers to reduce immune-mediated damage while maintaining tolerance, motivating further functional and translational studies in transplantation and other immune-mediated conditions.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 4","pages":"Article 111687"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico design of a therapeutic multi-epitope peptide candidate vaccine against rheumatoid arthritis","authors":"Azadeh Mohammadi Sepahvand ,&nbsp;Nasrin Azarbani ,&nbsp;Fateme Zare ,&nbsp;Manica Negahdaripour ,&nbsp;Ali Dehshahri","doi":"10.1016/j.humimm.2025.111654","DOIUrl":"10.1016/j.humimm.2025.111654","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the joints, resulting in inflammation, swelling, and pain, ultimately impacting patients’ quality of life and causing premature death. TNF-α, regulated by the NF-κB transcription factor, is a key cytokine implicated in tissue destruction and disease progression. Both TNF-α and the NF-κB receptor ligand (RANKL) are considered significant targets in the treatment of RA. Due to the limitations of current therapeutic strategies in providing safe and effective long-term healing, there is a clear need for novel therapeutic interventions, including vaccine development. This study aims to design an innovative multi-epitope polypeptide vaccine targeting RA through computational methods. To achieve this goal, epitope sequences from TNF-α and RANKL were predicted using three servers. Adjuvants CTxB, PADRE, and B29 were then incorporated with appropriate linkers. The structure underwent several analyses to assess physicochemical properties, immunogenicity, and allergenicity using various servers. The designed protein showed slightly hydrophilic characteristics with a negative Gravy index and a pI of 8.20. Additionally, with an instability index below 40, the protein demonstrates stability, which is crucial for the vaccine’s effectiveness. To predict the 3D structure, I-TASSER and trRosetta servers were utilized, and the best models underwent refinement using the GalaxyRefine server. Validation of the refined models was performed by the ProSA-web and Ramachandran plot analysis, and the best model was determined. Ultimately, the results of the conformational B-cell epitope prediction of the final model suggested that the designed vaccine can effectively trigger the humoral immune response. The combination of ten epitopes from TNF-α and RANKL linked with CTxB, PADRE, and B29 adjuvants presented a promising therapeutic candidate vaccine for RA.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 3","pages":"Article 111654"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947946","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":"A multipronged Tα1 reset of CD8+ T cell cytotoxicity against breast cancer","authors":"Smriti Mishra ,&nbsp;Gaurang Telang ,&nbsp;Anurag Sureshbabu ,&nbsp;Samruddhi Kulkarni ,&nbsp;Senthil Thayagrajan ,&nbsp;A.W Santhosh Kumar ,&nbsp;Rajshri Singh","doi":"10.1016/j.humimm.2026.111678","DOIUrl":"10.1016/j.humimm.2026.111678","url":null,"abstract":"<div><div>Thymosin α1 (Tα1) is an endogenous thymic peptide that enhances immune competence through activation of T cells, dendritic cells, and innate immune pathways. However, its direct impact on CD8⁺ T cell–mediated antitumor immunity in breast cancer remains unclear. In this study, CD8⁺ T cells isolated from peripheral blood of ten healthy donors were cultured under unstimulated, CD3/CD28-stimulated, Tα1-treated, or exhaustion–rescue conditions to evaluate cytotoxic activity against MDA-MB-231 breast cancer cells and CD44⁺ cancer stem-like cells (CD44⁺ CSC-like cells). Tα1 significantly enhanced CD8⁺ T cell–mediated apoptosis, suppressed tumor cell proliferation, and increased granzyme B secretion beyond CD3/CD28 stimulation alone. In exhausted T cells, Tα1 partially restored effector function and reduced PD-1, TIM-3, and LAG-3 expression. Complementary transcriptomic analysis using a compact four-gene Tα1 Response Index (Tα1-RI: TLR9, TLR2, IRF1, NLRC5) in TCGA-BRCA (n = 1,112) confirmed positive correlations with antigen presentation and cytotoxic programs and enrichment in CD8-like T cells in single-cell datasets. Collectively, these findings demonstrate that Tα1 enhances CD8⁺ T cell cytotoxicity while alleviating exhaustion, supporting its potential as an adjunct immunomodulator for improving immune surveillance in breast cancer.</div></div>","PeriodicalId":55047,"journal":{"name":"Human Immunology","volume":"87 3","pages":"Article 111678"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079158","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}