Critical reviews in immunology最新文献

{"title":"Chronic Hepatitis B: Current Understanding and Clinical Implications of Immune Exhaustion.","authors":"Yue Chen, Fei Huang, Meifang Han","doi":"10.1615/CritRevImmunol.2026061090","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2026061090","url":null,"abstract":"<p><p>Chronic hepatitis B (CHB) infection leads to progressive dysfunction and exhaustion of antiviral immune cells, which is a primary obstacle to clinical cure. Although the phenotypic hallmarks of exhausted T cells are well described, the hierarchical trajectory, subset-specific heterogeneity, and underlying mechanisms of exhaustion across the full spectrum of immune cells in the unique hepatic microenvironment remain poorly defined. This review provides a comprehensive and critical synthesis of recent advances in immune exhaustion during CHB. We delineate the common and distinct exhaustion programs among T, B, and natural killer cells, highlighting the pivotal roles of transcription factors and metabolic dysregulation. Furthermore, we critically evaluate the limitations of current evidence and pinpoint critical knowledge gaps, such as the heterogeneity of non-classical exhausted subsets and the liver-resident immune compartment. By framing these findings within a critical and comparative context, this review not only updates our understanding of immune exhaustion but also proposes a roadmap for developing more precise immunotherapies aimed at achieving a functional cure for CHB.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 3","pages":"23-44"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Dendritic Cells: Transforming the Impact of Cancer Immunotherapy.","authors":"Saleemulla Mahammad, Lu Chen, Anahid Jewett, Kawaljit Kaur","doi":"10.1615/CritRevImmunol.2025061548","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2025061548","url":null,"abstract":"<p><p>Aggressive tumors are treated with surgery, radiation, chemotherapy, targeted therapy, and various immunotherapies. Cancer immunotherapies under investigation encompass monoclonal antibodies, including checkpoint inhibitors, bispecific antibodies, and T cell redirecting antibodies, as well as gene-modified cell therapies such as CAR-T cells, donor lymphocyte infusions (DLI), antigen-specific DLI, and TCR-engineered T cells. While dendritic cell (DC)-based vaccines derived from peripheral blood have shown promise in preclinical studies, clinical trials have been less effective. Recently, a novel allogeneic DC vaccine has been developed using CD34+ hematopoietic stem cells (HSCs), which are engineered to overexpress CD93, CD40 ligand (CD40L), and CXCL13, thereby enhancing immune activation and improving scalability and effectiveness. This approach has shown potential in controlling tumor growth by stimulating the immune system in preclinical studies. This commentary highlights the promise of engineered allogeneic DC vaccines, their benefits over autologous methods, and the challenges of clinical translation. Combining this DC vaccine with checkpoint inhibitors and refining its design could make it a game-changing off-the-shelf cancer therapy.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 4","pages":"45-51"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secreted Phosphoprotein 1 Represents a Therapeutic Target that Promotes the Progression of Ovarian Cancer by Driving M2 Macrophage Infiltration.","authors":"Xiaorong Yang, Hong Zhu, Xia Zou, Qi Chen","doi":"10.1615/CritRevImmunol.2026061544","DOIUrl":"10.1615/CritRevImmunol.2026061544","url":null,"abstract":"<p><strong>Background: </strong>The substantial infiltration of M2 macrophages in ovarian cancer (OC) signifies a poor prognosis, although the precise mechanisms remain unclear. The pivotal role played by Secreted phosphoprotein 1 (SPP1)-regulated macrophage polarization is evident. This study seeks to validate the role of SPP1 and macrophages within the OC tumor microenvironment (TME), potentially laying the groundwork for therapeutic approaches in ovarian cancer.</p><p><strong>Methods: </strong>Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we analyzed the immune infiltration characteristics in OC and unearthed the functions of macrophages. Additionally, we conducted immunohistochemistry (IHC) analysis to assess the expression of SPP1 and CD206 in OC tissues patients. Furthermore, we utilized flow cytometry to analyze the infiltration and polarization of CD206-positive cells. Subsequently, we employed ELISA to investigate SPP1 secretion and Western blot analysis to assess ARG1 protein expression. Next, transwell assays were utilized to evaluate the invasive capabilities of macrophages following SPP1 intervention. Finally, EDU assays were performed to analyze the proliferative capacity of OC cells.</p><p><strong>Results: </strong>We discovered that the infiltration of SPP1+ macrophages was a distinctive feature of OC TME. Our findings confirmed the high expression of CD206 in OC, along with abundant SPP1 expression in tissues exhibiting high CD206 levels. Furthermore, this association correlated closely with worse tumor staging, ascites, HRD mutations, and peritoneal metastasis, suggesting a poor prognosis associated with SPP1+CD206 infiltration. Additionally, we observed that lactate regulates the secretion of SPP1. Moreover, SPP1-high macrophages could promote the proliferation of ovarian cancer cells.</p><p><strong>Conclusion: </strong>Our study identified the role of SPP1+macrophage in OC which may accelerated the metastasis and proliferation of OC.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 2","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148146071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusion Gene EPHB4-MET Driven by HOXA9 and Exerted Oncogenic Activity in Non-Small Cell Lung Cancer.","authors":"Wenjia Xia, Wenjing Zhu, Dongjie Feng, Youtao Xu, Tongyan Liu, Lin Xu","doi":"10.1615/CritRevImmunol.2026061678","DOIUrl":"10.1615/CritRevImmunol.2026061678","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is a type of lung cancer with high mortality. Mesenchymal-to-epithelial transition (MET) fusions are present in NSCLC and are associated with tumorigenesis. The Ephrin type-B receptor 4 (EPHB4)-MET fusion gene is a recently discovered gene, and there is a lack of research on its oncogenicity and driving mechanisms. In this study, we focused on the oncogenic properties and mechanism of the EPHB4-MET fusion gene.</p><p><strong>Methods: </strong>To create EPHB4-MET gene fusion cells, BEAS-2B cells were infected with lentivirus harboring EPHB4-MET. The expression efficiency was measured using reverse-transcriptase polymerase chain reaction (RT-PCR). Subsequently, cell counting kit-8 (CCK-8), crystal violet staining, and transwell assays were performed to investigate the oncogenicity of EPHB4-MET gene fusion. Finally, dual luciferase assay and chromatin immunoprecipitation (ChIP) were used to probe the binding of homeobox domain transcription factor A9 (HOXA9) to the EPHB4 promoter.</p><p><strong>Results: </strong>EPHB4-MET expression increased after infection with lentivirus, indicating that the gene fusion cell construction was successful. In addition, EPHB4-MET promoted MET activation of the downstream AKT pathway. Genes harboring EPHB4-MET significantly promoted cell proliferation, cell migration, and invasion. Subsequent research showed that via binding to the EPHB4 promoter region, HOXA9 induced the expression of EPHB4-MET, and knockdown of HOXA9 inhibited EPHB4-MET-induced oncogenic properties.</p><p><strong>Conclusion: </strong>In this study, we demonstrated that HOXA9 drove the expression of the fusion gene EPHB4-MET and exerted a tumorigenesis signature. HOXA9 may be a useful target for both diagnosis and treatment in patients with EPHB4-MET fusion genes in lung cancer.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 2","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148146040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomic Analysis Reveals ISG15 as a Key Regulator of Macrophage-Mediated Inflammation Driving Primary Sjögren's Syndrome Progression.","authors":"Yajing Chao, Jian Dong, Kunting Chen, Yalu Fu","doi":"10.1615/CritRevImmunol.2025060877","DOIUrl":"10.1615/CritRevImmunol.2025060877","url":null,"abstract":"<p><strong>Objectives: </strong>Primary Sjögren's syndrome (pSS) is characterized by molecular heterogeneity and immune-metabolic dysregulation. This study aimed to identify diagnostic biomarkers and characterize monocyte-macrophage differentiation trajectories in pSS.</p><p><strong>Methods: </strong>Bulk RNA-seq data were first batch-corrected and subjected to differential expression analysis, immune infiltration profiling, and weighted gene co-expression network analysis (WGCNA) to identify key gene modules. For single-cell RNA-seq, 42,157 salivary gland cells were clustered and annotated; Monocle3 pseudotime analysis reconstructed the monocyte-macrophage differentiation trajectory, and CellChat quantified intercellular signaling networks. Candidate immune-metabolism biomarkers were then screened by integrating WGCNA results with three machine-learning algorithms, LASSO regression, SVM-RFE, and random forest, and validated in the external GSE84844 cohort. Finally, functional relevance was tested in PMA-induced THP-1 macrophages by knocking down ISG15 and measuring effects on NF-κB activation and secretion of TNF-α and IL-1β.</p><p><strong>Results: </strong>Pseudotime analysis delineated a monocyte-to-macrophage differentiation axis and pinpointed 182 dynamic marker genes. Integrated machine-learning and network analysis highlighted four immune-metabolism genesISG15, OAS1, LAP3, and PARP9each achieving AUC > 0.80 in the GSE84844 validation set. In vitro, ISG15 knockdown markedly attenuated NF-κB activation and reduced TNF-α/IL-1β release, confirming its pivotal role in pSS-associated inflammation.</p><p><strong>Conclusions: </strong>This integrated transcriptomic analysis highlights key monocyte-macrophage trajectories and identifies four robust immune-metabolism biomarker candidates for pSS diagnosis. Functional validation of ISG15 suggests it plays a pivotal role in driving macrophage-mediated inflammatory responses in pSS.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 1","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}