Clinical immunology最新文献

Clinical immunology lessons from failed α-Synuclein and Tau immunotherapies: A roadmap for combination strategies in Alzheimer's disease. α-突触核蛋白和Tau蛋白免疫治疗失败的临床免疫学教训：阿尔茨海默病联合治疗策略的路线图。

IF 4.1 3区医学

Clinical immunology Pub Date : 2026-08-29 DOI: 10.1016/j.clim.2026.110777

Ahmed M Abdelaziz, Fatma S Eltyar

{"title":"Clinical immunology lessons from failed α-Synuclein and Tau immunotherapies: A roadmap for combination strategies in Alzheimer's disease.","authors":"Ahmed M Abdelaziz, Fatma S Eltyar","doi":"10.1016/j.clim.2026.110777","DOIUrl":"10.1016/j.clim.2026.110777","url":null,"abstract":"<p><p>Anti-amyloid-β monoclonal antibodies have established immunotherapy as a viable approach for Alzheimer's disease, yet all α-synuclein and tau antibodies tested to date have failed clinically. These setbacks offer invaluable immunology lessons reshaping next-generation therapeutic development. Four key lessons emerge: epitope specificity determines outcomes, with mid-domain and microtubule-binding region antibodies showing promise over failed N-terminal approaches; biomarker-driven stratification using p-tau217 and AI algorithms can unmask efficacy in rapid progressors; most patients harbor mixed proteinopathies, rendering monotherapy insufficient and mandating combination immunotherapy; and neuroinflammation, particularly NLRP3 activation and microglial dysfunction, represents a convergent pathway targetable independently of upstream triggers. Emerging approaches include conformation-specific antibodies, protein-protein interaction inhibitors, and immune checkpoint targeting, such as anti-SIGLEC-10, to restore phagocytosis. These insights inform biomarker-enriched trials and combination regimens, although clinical evidence for specific combinations remains limited and requires validation. The systems framework targeting aggregation, neuroinflammation, and immunity offers a promising paradigm yet awaits empirical testing.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110777"},"PeriodicalIF":4.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TIM-3 as a therapeutic target in anaplastic thyroid carcinoma: Preclinical and transcriptomic evidence supporting a new immunotherapy avenue. TIM-3作为间变性甲状腺癌的治疗靶点：临床前和转录组学证据支持新的免疫治疗途径。

IF 4.1 3区医学

Clinical immunology Pub Date : 2026-08-28 DOI: 10.1016/j.clim.2026.110761

Monikongkona Boruah, Riyaz Ahmad Mir, Sameer Rastogi, Kapil Sikka, Shipra Agarwal

{"title":"TIM-3 as a therapeutic target in anaplastic thyroid carcinoma: Preclinical and transcriptomic evidence supporting a new immunotherapy avenue.","authors":"Monikongkona Boruah, Riyaz Ahmad Mir, Sameer Rastogi, Kapil Sikka, Shipra Agarwal","doi":"10.1016/j.clim.2026.110761","DOIUrl":"https://doi.org/10.1016/j.clim.2026.110761","url":null,"abstract":"<p><p>We recently characterized the microenvironment of Anaplastic Thyroid Carcinoma (ATC) as immune-exhausted, rich in TIM-3-expressing exhausted cytotoxic T lymphocytes (CTLs). PD-1 was notably the least frequently expressed immune checkpoint (ICP). The results provided a potential explanation for the limited efficacy of anti-PD-1/PD-L1 immunotherapy, highlighting TIM-3 as another promising target. This pilot study further evaluated the potential efficacy of targeting TIM-3 in ATC as a therapeutic strategy in an in vitro model. A co-culture model of ATC cell line 8505C with exhausted TIM-3<sub>+ve</sub>/PD-1<sub>+ve</sub> CTLs was established and treated with anti-TIM-3 and anti-PD-1 antibodies, alone and in combination. Antibody efficacy was evaluated using flow cytometry, measuring Granzyme B and Perforin for CTL cytotoxic activity, and Annexin V and propidium iodide for tumor cell death. Additionally, differential gene expression before and after ICP blockade was analyzed using the NanoString nCounter Immune-oncology Panel. Both individual and combined antibody treatments enhanced CTL cytotoxicity and promoted tumor cell death. Interestingly, ICP inhibition induced an upregulation of immune-activating pathways and downregulation of genes associated with tumor progression. These findings support the potential of TIM-3 blockers as an alternative to or in combination with anti-PD-1 therapy, thereby providing a rationale for further clinical investigation.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110761"},"PeriodicalIF":4.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma anti-ATP7A/ATP7B/COPT1 autoantibodies as potential biomarkers for breast cancer detection. 血浆抗atp7a /ATP7B/COPT1自身抗体作为乳腺癌检测的潜在生物标志物

IF 4.1 3区医学

Clinical immunology Pub Date : 2026-08-27 DOI: 10.1016/j.clim.2026.110764

Peiqi Yu, Tingzun Nie, Aichen Liu, Lulu Zhang, Wenke Sun, Yihao Liang, Yunhui Qu, Liping Dai, Jingjing Liu

引用次数: 0

Aicardi-Goutières Syndrome caused by SAMHD1 mutation: Pathogenesis and Beyond SAMHD1突变引起的aicardii - gouti<e:1>综合征：发病机制及其他。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-02-08 DOI: 10.1016/j.clim.2026.110680

Yuhan Li , Songcheng Ying

引用次数: 0

Plasma anti-DLAT autoantibody as a novel diagnostic biomarker in breast cancer 血浆抗dlat自身抗体作为一种新的乳腺癌诊断标志物。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.clim.2026.110678

Qianwei Zhao , Ludan Zhang , Peiqi Yu , Jingjing Liu , Tingjiang He , Yunhui Qu , Anqi Cheng , Fang Xu , Liping Dai

{"title":"Plasma anti-DLAT autoantibody as a novel diagnostic biomarker in breast cancer","authors":"Qianwei Zhao , Ludan Zhang , Peiqi Yu , Jingjing Liu , Tingjiang He , Yunhui Qu , Anqi Cheng , Fang Xu , Liping Dai","doi":"10.1016/j.clim.2026.110678","DOIUrl":"10.1016/j.clim.2026.110678","url":null,"abstract":"<div><h3>Background</h3><div>Tumor-associated autoantibodies (TAAbs) represent promising biomarkers for tumor diagnosis. This study aimed to evaluate the prognostic value of anti- Dihydrolipoamide <em>S</em>-acetyltransferase (DLAT) AAb in breast cancer (BC).</div></div><div><h3>Methods</h3><div>Levels of plasma anti-DLAT AAb were measured by ELISA in a total of 1013 samples from BC patients, patients with benign breast nodules (BN), and healthy controls (NC). Western blot was performed to confirm the ELISA results. The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were used to analyze the expression levels of DLAT in tumor and normal breast tissues from BC patients.</div></div><div><h3>Results</h3><div>Plasma anti-DLAT AAb levels were decreased in BC compared to NC and BN, achieving AUCs of 0.803 (<em>P</em> < 0.0001) and 0.591 (<em>P</em> < 0.0001), respectively. Among individuals under 45 years old, anti-DLAT AAb showed high power in distinguishing BC and BC at early-stage from NC, yielding an AUC of 0.873 (<em>P</em> < 0.0001) and 0.845 (<em>P</em> < 0.0001). Besides, anti-DLAT AAb distinguished BC from BN with an AUC of 0.617 (<em>P</em> = 0.0016) in individuals under 45 while there was no difference between them above 45. Combining anti-DLAT AAb with CEA improved the AUCs to 0.824 (<em>P</em> < 0.0001) and 0.623 (<em>P</em> < 0.0001) for distinguishing BC from NC and BN. This combination also achieved higher AUCs of 0.891 (<em>P</em> < 0.0001) and 0.635 (<em>P</em> = 0.0003) for distinguishing BC from NC and BN among individuals under 45 years old.</div></div><div><h3>Conclusions</h3><div>These findings suggest that anti-DLAT AAb shows potential for BC diagnosis, especially among individuals under 45 years old. Besides, multicenter validation should be carried out to confirm this finding in the future.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110678"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Life towards death: Neutrophils in immune-mediated inflammatory diseases 从生命走向死亡：免疫介导的炎症性疾病中的中性粒细胞。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 10.1016/j.clim.2026.110667

Jinkai Liang , Jiaqi Wang , Hui Fang , Xin Tang, Ke Xue, Wanting Liu, Shuai Shao, Gang Wang

引用次数: 0

HIV patients with poor immune recovery show exhausted CD4+ stem cell memory cells and impaired COVID-19 vaccine response 免疫恢复较差的HIV患者CD4+干细胞记忆细胞耗竭，COVID-19疫苗应答受损。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-02-02 DOI: 10.1016/j.clim.2026.110676

Susanna Scaglioni , Andrea Lombardi , Giacomo M. Butta , Giorgio Bozzi , Matteo Centazzo , Bianca Mariani , Antonio Muscatello , Patrizia Bono , Lorena Donnici , Matteo Conti , Riccardo Nodari , Annapaola Callegaro , Edoardo Scarpa , Renata Grifantini , Sergio Abrignani , Raffaele De Francesco , Andrea Gori , Alessandra Bandera , Lara Manganaro

{"title":"HIV patients with poor immune recovery show exhausted CD4+ stem cell memory cells and impaired COVID-19 vaccine response","authors":"Susanna Scaglioni , Andrea Lombardi , Giacomo M. Butta , Giorgio Bozzi , Matteo Centazzo , Bianca Mariani , Antonio Muscatello , Patrizia Bono , Lorena Donnici , Matteo Conti , Riccardo Nodari , Annapaola Callegaro , Edoardo Scarpa , Renata Grifantini , Sergio Abrignani , Raffaele De Francesco , Andrea Gori , Alessandra Bandera , Lara Manganaro","doi":"10.1016/j.clim.2026.110676","DOIUrl":"10.1016/j.clim.2026.110676","url":null,"abstract":"<div><div>Vaccination triggers both humoral and cellular immune responses, generating memory T cells that ensure long-term protection. Among these, stem cell-like memory T cells (T<sub>SCM</sub>) are crucial for durable immunity due to their self-renewal and multipotency. In people with HIV (PWHIV), vaccine-induced responses can be weakened by persistent immune dysfunction. In this study, we longitudinally analyzed T cell memory responses following mRNA-1273 vaccination in PWHIV. Individuals with incomplete immune reconstitution (CD4<sup>+</sup> < 500 cells/μL, CD4/CD8 < 0.4) showed reduced frequencies of Spike-specific CD4<sup>+</sup> T<sub>SCM</sub>, lower levels of TCF-1 and higher expression of immune checkpoint molecules. We identified a subset of PD-1<sup>+</sup>TIGIT<sup>+</sup> CD4<sup>+</sup> T<sub>SCM</sub> and T<sub>CM</sub> cells that phenotypically resemble CD8<sup>+</sup> exhausted-like progenitors (T<sub>PEX</sub>) and are enriched in PWHIV with poor immune recovery. Modulation of the Wnt/mTORs pathway via GSK3β inhibition restored TCF-1 expression and partially rescued antigen responsiveness, highlighting a potential strategy to improve vaccine efficacy in PWHIV.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110676"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated single cell RNA sequencing and flow cytometry analysis identifies elevated S100A6+ and S100A8+ myeloid subsets in pancreatic ductal adenocarcinoma 综合单细胞RNA测序和流式细胞术分析发现胰腺导管腺癌中S100A6+和S100A8+髓系亚群升高。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-01-21 DOI: 10.1016/j.clim.2026.110665

Afshin Derakhshani , Roberta Di Fonte , Letizia Porcelli , Fatemeh Nejadi Orang , Mahdi Abdoli Shadbad , Adib Miraki Feriz , Hossein Safarpour , Antoine Dufour , Behzad Baradaran , Angela Calabrese , Mario Testini , Riccardo Memeo , Giovanna Di Meo , Leonardo Vincenti , Sonali Bhardwaj , Vito Racanelli , Nicola Silvestris , Oronzo Brunetti , Amalia Azzariti

{"title":"Integrated single cell RNA sequencing and flow cytometry analysis identifies elevated S100A6+ and S100A8+ myeloid subsets in pancreatic ductal adenocarcinoma","authors":"Afshin Derakhshani , Roberta Di Fonte , Letizia Porcelli , Fatemeh Nejadi Orang , Mahdi Abdoli Shadbad , Adib Miraki Feriz , Hossein Safarpour , Antoine Dufour , Behzad Baradaran , Angela Calabrese , Mario Testini , Riccardo Memeo , Giovanna Di Meo , Leonardo Vincenti , Sonali Bhardwaj , Vito Racanelli , Nicola Silvestris , Oronzo Brunetti , Amalia Azzariti","doi":"10.1016/j.clim.2026.110665","DOIUrl":"10.1016/j.clim.2026.110665","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, underscoring the need for minimally invasive biomarkers to support patient stratification and disease monitoring. In this study, we aimed to identify PDAC-associated immune signatures by reanalyzing a single-cell RNA-sequencing dataset and to validate key findings using flow cytometry in an independent cohort predominantly composed of advanced-stage PDAC. Analysis of peripheral blood mononuclear cells from patients with PDAC and healthy donors revealed increased expression of S100A6, S100A8, and S100A12, particularly within monocytes and dendritic cells. These transcriptional changes were confirmed at the protein level, demonstrating enrichment of S100A6<sup>+</sup> monocytes, S100A6<sup>+</sup>/S100A8<sup>+</sup> DCs, activated monocytes, and plasmacytoid DCs in PDAC. Univariate ROC analyses identified S100A6<sup>+</sup> plasmacytoid DCs, S100A8<sup>+</sup> plasmacytoid DCs, and CD14<sup>+</sup>CD86<sup>+</sup>S100A8<sup>+</sup> monocytes as candidate PDAC-associated immune features. However, further validation incorporating benign pancreatic conditions and multivariable modeling is required before conclusions can be drawn regarding diagnostic specificity and clinical applicability.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110665"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of neutrophil extracellular traps via the FGF19/ERK/IL-8 axis enhances immune therapy in MSS colorectal cancer 通过FGF19/ERK/IL-8轴抑制中性粒细胞胞外陷阱可增强MSS结直肠癌的免疫治疗。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 10.1016/j.clim.2026.110664

Yiyang Wu , Jintian Wang , Pengcheng Wang , Qiwei Chen , Jing Jia , Yan Liu , Yao Chen , Kai Ye

{"title":"Inhibition of neutrophil extracellular traps via the FGF19/ERK/IL-8 axis enhances immune therapy in MSS colorectal cancer","authors":"Yiyang Wu , Jintian Wang , Pengcheng Wang , Qiwei Chen , Jing Jia , Yan Liu , Yao Chen , Kai Ye","doi":"10.1016/j.clim.2026.110664","DOIUrl":"10.1016/j.clim.2026.110664","url":null,"abstract":"<div><h3>Background</h3><div>Microsatellite-stable colorectal cancer (MSS CRC) resists immune checkpoint inhibitors. FGF19's immunomodulatory role in MSS CRC remains unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analyzed FGF19 expression and CD8<sup>+</sup> T-cell infiltration. CRC cells co-cultured with neutrophils (dHL-60) assessed chemotaxis and NET markers. LDH assay, ELISA, and CFSE staining measured CD8<sup>+</sup> T-cell activity. CCK-8, EdU, Transwell, and flow cytometry assessed CRC phenotypes. Mouse model tested PD-1 antibody and FGFR4 inhibitor BLU-9931.</div></div><div><h3>Results</h3><div>FGF19 was upregulated in non-immunogenic MSS CRC, negatively correlating with CD8<sup>+</sup> T cells. Elevated FGF19 enhanced neutrophil chemotaxis and NET release, inhibiting CD8<sup>+</sup> T-cell cytotoxicity and proliferation while promoting malignant CRC behavior. Mechanistically, FGF19-FGFR4 signaling was associated with increased ERK pathway activity, elevated IL-8 levels, and NET formation. Blocking FGF19-FGFR4 enhanced PD-1 efficacy in MSS CRC.</div></div><div><h3>Conclusion</h3><div>The FGF19/ERK/IL-8 pathway contributed to NET formation in this model. Targeting this pathway represents a promising strategy to boost immunotherapy in MSS CRC.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110664"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated asprosin expression exacerbates synovial inflammation by PPAR-γ-dependent mechanisms in rheumatoid arthritis 类风湿关节炎中asprosin表达升高通过PPAR-γ依赖机制加剧滑膜炎症。

IF 3.8 3区医学

Clinical immunology Pub Date : 2026-04-01 Epub Date: 2026-02-02 DOI: 10.1016/j.clim.2026.110677

Shu-Zhen Xu , Sha-Sha Tao , Peng Wang , Hai-Fen Wei , Yu-Tong Tan , Jian Tang , Zhu Chen , Hai-Feng Pan

{"title":"Elevated asprosin expression exacerbates synovial inflammation by PPAR-γ-dependent mechanisms in rheumatoid arthritis","authors":"Shu-Zhen Xu , Sha-Sha Tao , Peng Wang , Hai-Fen Wei , Yu-Tong Tan , Jian Tang , Zhu Chen , Hai-Feng Pan","doi":"10.1016/j.clim.2026.110677","DOIUrl":"10.1016/j.clim.2026.110677","url":null,"abstract":"<div><div>Asprosin, a recently identified adipokine involved in metabolic and inflammatory processes. The case-control study was conducted to explore how asprosin is involved in the pathogenesis of rheumatoid arthritis (RA). 205 RA patients and 205 healthy controls were included, and MH7A cells were used for <em>in vitro</em> studies. Plasma asprosin was elevated in RA patients [11.4 (8.2, 15.6) ng/mL] compared to healthy controls [9.3 (7.5, 10.5) ng/mL] (<em>Z</em> = 5.978, <em>P</em> < 0.001) and exhibited moderate diagnostic accuracy (AUC = 0.67). Asprosin significantly enhanced the proliferation of synovial fibroblasts and upregulated the proinflammatory cytokines, while promoting their migratory and invasive capacities. TNF-α led to a marked downregulation of PPAR-γ, which was associated with increased asprosin levels, treatment with rosiglitazone effectively attenuated asprosin overproduction. Elevated circulating asprosin levels serve as an independent risk factor for RA and demonstrate promising diagnostic potential. PPAR-γ-mediated overexpression of asprosin contributes to synovial fibroblast dysfunction, suggesting a pathogenic role in RA development.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110677"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0