Immunotherapy advances最新文献

{"title":"Regulatory B cells promote the immunosuppressive microenvironment and progression of clear cell renal cell carcinoma.","authors":"Qintao Ge, Siqi Zhou, Jiahe Lu, Shiqi Ye, Aihetaimujiang Anwaier, Xi Tian, Yonghao Chen, Hailiang Zhang, Dingwei Ye, Wenhao Xu","doi":"10.1093/immadv/ltaf013","DOIUrl":"10.1093/immadv/ltaf013","url":null,"abstract":"<p><strong>Background: </strong>Regulatory B cells (Bregs) are critical mediators of immune modulation and tumor progression. However, their prognostic relevance and mechanistic roles in clear cell renal cell carcinoma (ccRCC) remain insufficiently explored.</p><p><strong>Methods: </strong>A comprehensive pancancer strategy was implemented to assess the prognostic role of Breg cells. Spatial transcriptomics, multiplex immunofluorescence (mIF), and immunohistochemistry were performed to investigate Breg localization and immunosuppressive functionality in ccRCC. A machine learning-derived Breg signature (CMLBregS) was established and validated for risk stratification and immune profiling.</p><p><strong>Results: </strong>Elevated Breg signatures were prominently observed in ccRCC and were associated with advanced T stage, higher tumor grades, and decreased progression-free survival. Spatial transcriptomics and mIF revealed that CD20⁺CD23⁺IL10V Breg cells exert immunosuppressive effects, with or without of the presence of tertiary lymphoid structures. The CMLBregS, comprising 16 Breg-related genes, effectively stratified built a binary classification system. A high-CMLBregS score was linked to an immunosuppressive TME characterized by upregulated IL-10 and TGF-β production, suppression of lymphocyte activation, reduced T cell proliferation, and dampened innate immune responses. Patients with higher CMLBregS scores demonstrated significantly worse clinical outcomes across multiple cohorts. Among CMLBregS-related genes, IRF4 emerged as a key prognostic marker, strongly correlating with IL-10 and PDCD1 expression. Notably, patients with elevated CMLBregS scores exhibited poorer responses to immune checkpoint blockade therapy and more aggressive disease progression during immunotherapy.</p><p><strong>Conclusion: </strong>This study underscores the pivotal role of Bregs in promoting immune suppression and poor prognosis in ccRCC. The CMLBregS model offers a robust prognostic tool, identifies patients less likely to benefit from immunotherapy, and highlights IRF4 as a potential alternative target. These findings provide a foundation for future strategies aimed at overcoming Breg-mediated immunosuppression in ccRCC.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf013"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of regulatory B cells in autoimmune diseases: implications for immune equilibrium and therapeutic strategies.","authors":"Haozhen Yan, Jing He, Xiang Lin","doi":"10.1093/immadv/ltaf020","DOIUrl":"10.1093/immadv/ltaf020","url":null,"abstract":"<p><p>Regulatory B cells (Bregs) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. However, in autoimmune conditions, the quantity and function of Bregs are often impaired, leading to pro-inflammatory microenvironment and immune dysregulation. This review provides an in-depth examination of how Bregs are affected in various autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, autoimmune diabetes, and other autoimmune conditions. By summarizing the alterations in Bregs phenotype and function in these specific diseases, we conclude that the Bregs response is complex and variable, showing inconsistent trend across different diseases or even within the same disease. Thus, understanding the heterogeneous nature of Bregs in the autoimmune pathogenesis facilitates novel therapeutic strategies to re-establish immune equilibrium.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf020"},"PeriodicalIF":4.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLUT5 armouring enhances adoptive T-cell therapy anti-tumour activity under glucose-limiting conditions.","authors":"Robert Page, Olivier Martinez, Daniel Larcombe-Young, Eva Bugallo-Blanco, Sophie Papa, Esperanza Perucha","doi":"10.1093/immadv/ltaf018","DOIUrl":"10.1093/immadv/ltaf018","url":null,"abstract":"<p><strong>Background: </strong>Cancer immunotherapy with engineered T cells has become a standard treatment for certain haematological cancers. However, clinical trial outcomes for solid tumours are significantly lagging. A primary challenge in solid tumours is the lack of essential metabolites in the tumour microenvironment, such as glucose, due to poor vascularization and competition with tumour cells.</p><p><strong>Methods: </strong>To address this, we modified T cells to use fructose as an alternative energy source by introducing ectopic GLUT5 expression.</p><p><strong>Results: </strong>We show that \"GLUT5-armored\" T cells, engineered with either chimeric antigen receptors (CARs) or an ectopic T-cell receptor (TCR), achieve enhanced anti-tumour activity in low-glucose environments in both <i>in vitro</i> and <i>in vivo</i> models.</p><p><strong>Conclusion: </strong>This straightforward modification is compatible with current clinical approaches and may improve the efficacy of T-cell therapies for solid tumours.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf018"},"PeriodicalIF":4.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12201985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from the bottom-up development of LGR5-targeting immunotherapeutics.","authors":"Nico Mueller, Marc Andrew de la Roche, Maike de la Roche","doi":"10.1093/immadv/ltaf017","DOIUrl":"10.1093/immadv/ltaf017","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a transcriptional target gene of the Wnt signalling pathway, is overexpressed in multiple cancers, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B acute lymphoblastic leukaemia (pre-B ALL) and has emerged as a promising therapeutic target. Here, we reflect on the bottom-up development of a novel α-LGR5 therapeutic antibody we have recently reported, into a palette of LGR5-targeting immunotherapeutic modalities: antibody-drug conjugates (ADCs), bispecific T cell engagers (bispecific engagers), and chimeric antigen receptor (CAR) T cells. The α-LGR5 antibody is highly specific and accurately detects LGR5 protein expression levels, enabling its use as a prognostic biomarker for identifying LGR5⁺ tumour types. Preclinical studies road-testing the various α-LGR5-based modalities established potent and safe elimination of LGR5-expressing cancer cells <i>in vitro</i> and efficacy in a mouse model of human cancer <i>in vivo</i>. In this review, we discuss the utility of our antibody as the building block for a novel set of immunotherapeutics and highlight the importance of matching specific α-LGR5-based therapeutic modalities to individual tumour type and patient characteristics.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf017"},"PeriodicalIF":4.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing monocyte dynamics for treatment of multiple sclerosis; insights from experimental model studies.","authors":"Aqsa Bibi, Zhenjiang Yu, Lv Cui, Guiwen Yang","doi":"10.1093/immadv/ltaf003","DOIUrl":"https://doi.org/10.1093/immadv/ltaf003","url":null,"abstract":"<p><p>Monocytes are central to the innate immune system's response to infection or injury. In murine, these cells are classified into distinct subsets: classical monocytes, defined by elevated Ly6C expression (Ly6C^hi), intermediate monocytes (Ly6C^int), and non-classical inflammatory monocytes, characterized by low Ly6C expression (Ly6C^low). Monocytes recruited to tissues differentiate into macrophages, which can be pro-inflammatory or anti-inflammatory, thereby influencing disease processes and outcomes. The principal function of classical monocytes is the mediation of pro-inflammatory reactions, whereas non-classical monocytes are associated with repair and anti-inflammatory processes, patrolling the lumen of the vessels. Growing evidence highlights the importance of monocytes in multiple sclerosis (MS), an autoimmune and neurodegenerative disease of the central nervous system (CNS). Recent studies indicate that modulation of the innate immune system, focusing specifically on the shift from Ly6C^hi to Ly6C^low monocytes, is an effective therapeutic strategy for neurodegenerative diseases, such as Alzheimer's and MS. This transition is crucial for switching the immune response from inflammation to tissue repair and inflammation resolution, emphasizing the plasticity of monocytes and their potential as targets in MS. This review differs from prior studies in that it focuses solely on animal models of MS, which either directly perturb or study monocytes, or where therapeutic approaches mediate their protective effects through monocytes. Such details permit a subtle comprehension of monocyte dynamics in the context of MS.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf003"},"PeriodicalIF":4.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer vaccine trial evaluations: immunobridging and potential immunological endpoints.","authors":"Ahmed Hussain, Benjamin Moxley-Wyles, Michael Bryan, Alex Gordon-Weeks, Ibrahem Al-Obaidi, Ciaran Sandhu, Lennard Lee","doi":"10.1093/immadv/ltaf016","DOIUrl":"10.1093/immadv/ltaf016","url":null,"abstract":"<p><p>Therapeutic cancer vaccines are an emerging class of immunotherapy, but challenges remain in effectively adapting approved vaccines to a growing number of adjuvants, combination therapies, and antigen-selection methods. Phase III clinical trials remain the gold standard in determining clinical benefit, but are slow and resource intensive, whilst radiological surrogates often fail to reliably predict clinical benefit. Using immunological surrogates of efficacy, deployed in 'immunobridging trials', could present a viable alternative, safely speeding up cancer vaccine development in a cost-effective manner. Whilst this approach has proven successful in infectious disease vaccines, identifying reliable immunological correlates of protection has proven difficult for cancer vaccines. Most clinical trials, which present the richest source of data to establish a correlate, rely on peripheral blood samples and standard immunoassays that are ill-equipped to capture the complexity of the vaccine-induced anti-tumour response. This review is the first to outline the importance and challenges of establishing immunological surrogates for cancer vaccines in the context of immunobridging trials, evaluating current immunoassay methods, and highlighting the need for techniques that can characterize tumour-infiltrating lymphocytes and the suppressive tumour microenvironment across a range of patients. The authors propose adapting trial designs for surrogate discovery, including combining phase I/II trials and the use of multi-omics approaches. Successful immunological surrogate development could enable future immunobridging trials to accelerate the optimization of approved cancer vaccines without requiring new phase III trials, promoting faster clinical implementation of scientific advances and patient benefits.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf016"},"PeriodicalIF":4.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge-based immune-therapeutic advances for transplantation and cancer.","authors":"Elizabeth Simpson","doi":"10.1093/immadv/ltaf014","DOIUrl":"10.1093/immadv/ltaf014","url":null,"abstract":"<p><p>Increased knowledge about immune responses to what is perceived as 'foreign' or 'non-self' has revealed extraordinary levels of complexity. Research uncovering these has the potential to optimise immunotherapy. Remarkable progress has been made in transplantation leading to much less acute rejection and a very significant increase in long-term survival. These and other beneficial results have been achieved by stepwise advances, using combinations of less toxic chemotherapies with biological immunosuppressive agents alongside innovatory surgical skills. However, rejection is the default pathway for entities deemed 'foreign', including mistaken suspects like autoantigens. For tumour immunotherapy the identification of <i>bona fide</i> tumour antigens recognised by B and/or T cell receptors has mushroomed but has yet to be optimised to take into account mutations leading to tumour evasion. We are now at the beginning of a road that looks more hopeful by being informed of the complexities. Basic and translational research between the late 1960s and now have yielded an extraordinarily rich harvest of new knowledge. More is to come, further insight is needed and new paradigms explored.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf014"},"PeriodicalIF":4.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lag3 and PD-1 pathways preferentially regulate NFAT-dependent TCR signalling programmes during early CD4⁺ T cell activation.","authors":"Lozan Sheriff, Alastair Copland, David A J Lecky, Reygn Done, Lorna S George, Emma K Jennings, Sophie Rouvray, Thomas A E Elliot, Elizabeth S Jinks, Lalit Pallan, David Bending","doi":"10.1093/immadv/ltaf015","DOIUrl":"https://doi.org/10.1093/immadv/ltaf015","url":null,"abstract":"<p><strong>Introduction: </strong>Lag3 and PD-1 are immune checkpoints that regulate T cell responses and are current immunotherapy targets. Yet how they function to control early stages of CD4⁺ T cell activation remains unclear.</p><p><strong>Methods: </strong>Here, we show that the PD-1 and Lag3 pathways exhibit layered control of the early CD4⁺ T cell activation process, with the effects of Lag3 more pronounced in the presence of PD-1 pathway co-blockade (CB). RNA sequencing revealed that CB drove an early NFAT-dependent transcriptional profile, including promotion of ICOS^hi T follicular helper cell differentiation.</p><p><strong>Results: </strong>NFAT pathway inhibition abolished CB-induced upregulation of NFAT-dependent co-receptors ICOS and OX40, whilst unaffecting the NFAT-independent gene <i>Nr4a1</i>. Mechanistically, Lag3 and PD-1 pathways functioned additively to regulate the duration of T cell receptor signals during CD4⁺ T cell re-activation. Phenotypic changes in peripheral blood CD4⁺ T cells in humans on anti-Lag3 and anti-PD-1 combination therapy revealed upregulation of genes encoding ICOS and OX40 on distinct CD4⁺ T cell subsets, highlighting the potential translational relevance of our findings.</p><p><strong>Conclusion: </strong>Our data therefore reveal that PD-1 and Lag3 pathways converge to additively regulate TCR signal duration and may preferentially control NFAT-dependent transcriptional activity during early CD4⁺ T cell re-activation.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf015"},"PeriodicalIF":4.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal glucose and lipid metabolism promotes disrupted differentiation of T and B cell subsets in Behçet's disease.","authors":"Minghao Li, Ping Li, Xin Wang, Lijie Wang, Guanmin Gao, Guosheng Jiang, Tingting Liu, Wei Lin","doi":"10.1093/immadv/ltaf010","DOIUrl":"https://doi.org/10.1093/immadv/ltaf010","url":null,"abstract":"<p><strong>Introduction: </strong>Behçet's disease (BD) is a chronic, systemic inflammatory condition characterized by recurrent immune dysregulation.</p><p><strong>Materials & methods: </strong>This study conducted a comprehensive analysis of immune cell subsets, metabolic markers, and their interplay in BD patients. Using multiparametric flow cytometry, we identified elevated Th1 cells, senescent CD8⁺ T cells, and abnormal B cell activation as hallmarks of the chronic inflammatory state in BD.</p><p><strong>Results: </strong>Despite immunotherapy, innate immune activation persisted, with increased mature NK cells, γδT1 cells, and conventional dendritic cells (cDCs), alongside reduced plasmacytoid dendritic cells (pDCs). Elevated glucose (GLU) and triacylglycerol (TAG) levels in BD patients correlated with increased Th1 cells, functional CD8⁺ T cells, and B cell activation. In vitro experiments demonstrated that GLU and TAG promote Th1 differentiation, CD8⁺ T cell activation, and B cell antibody production, revealing their role as drivers of immune dysregulation.</p><p><strong>Conclusion: </strong>These findings underscore the intricate relationship between metabolic dysregulation and immune dysfunction in BD, highlighting potential diagnostic and therapeutic targets. Our study provides critical insights into BD pathogenesis, offering a foundation for optimizing disease management and monitoring immune and metabolic markers for improved patient outcomes.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf010"},"PeriodicalIF":4.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra-tumoural RAMP1+ B cells promote resistance to neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma.","authors":"Hongyu Zhang, Yuchen Zhang, Pingjing Zhou, Yifan Guo, Liqun Jiang, Jie Gu","doi":"10.1093/immadv/ltaf012","DOIUrl":"10.1093/immadv/ltaf012","url":null,"abstract":"<p><strong>Introduction: </strong>The application of neoadjuvant immunotherapy in oesophageal squamous cell carcinoma (ESCC) reactivates anti-tumour immune responses and prolong postoperative survival. However, due to the heterogeneity of tumour microenvironment, limited patients have achieved pathological regression after treatment. The dual roles of B cells were recently highlighted in ESCC. The study aimed to investigate the role of B cell subclusters and the upstream signalling of B cell differentiation in ESCC resistant to immunotherapy.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was employed for ESCC specimens with distinct responses to neoadjuvant immunotherapy to map the landscape of intra-tumoural B cells.</p><p><strong>Results: </strong>A novel subset of neuropeptide receptor, receptor activity-modifying protein 1 (RAMP1) positive B cells was revealed to accumulate in ESCC that is resistant to neoadjuvant immunotherapy. Stimulated by nociceptor neurons secreting calcitonin gene-related peptide (CGRP), RAMP1(+) B cells exhibit an immunosuppressive phenotype. The elevated secretion of immune-regulating cytokines by RAMP1(+) B cells blunts the cytotoxicity of Cluster of Differentiation (CD)8(+) T cell and leads to tumour immune evasion. A combination of RAMP1 blocker and anti-Programmed cell death protein (PD)-1 therapies synergistically reinvigorated anti-tumour immunity, reducing tumour progression <i>in vitro</i>.</p><p><strong>Conclusion: </strong>The study suggests that RAMP1(+) B cells play a critical role in mediating resistance to neoadjuvant immunotherapy in ESCC. Targeting the CGRP-RAMP axis remodels B cells and enhance the efficacy of current immunotherapies, providing new strategies for overcoming treatment resistance.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf012"},"PeriodicalIF":4.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}