Immunotherapy advances最新文献

{"title":"Tumor cell spheroid-induced suppression of primary human cytotoxic T cells as a scalable <i>in vitro</i> model of exhaustion.","authors":"Amal Alsubaiti, Hanin Alamir, Lan Huynh, Tressan Grant, Abdullah Aljohani, Po Han Chou, Yiwei Shi, Maryam Alismail, Lydia R Mason, Andrew Herman, John S Bridgeman, Christopher J Holland, Christoph Wülfing","doi":"10.1093/immadv/ltaf023","DOIUrl":"10.1093/immadv/ltaf023","url":null,"abstract":"<p><strong>Background: </strong>Cytotoxic T lymphocytes (CTL) are key effectors in the antitumor immune response. However, their function is commonly suppressed in tumors in the form of exhausted CTL. Understanding mechanisms of suppression and of therapeutics to overcome them is of substantial basic and translational importance yet hindered by limited access to large numbers of exhausted CTL in vitro.</p><p><strong>Methods: </strong>Here we use three-dimensional tissue culture to generate primary human CTL with suppressed function. Using functional assays, a 21-antibody flow cytometry panel and determination of calcium signaling and CTL tumor cell couple maintenance, we have characterized their phenotype.</p><p><strong>Results: </strong>We show that these cells closely resemble exhausted CTL from tumors. For a better understanding of in vitro human primary CTL as key tools in therapeutic development, before and after induction of suppression, we have determined the dependence of CTL function on methodology of generation, antigen dose, and affinity across two T-cell receptors and multiple tumor cell lines. As a further determination of their phenotype, we have investigated the morphology and subcellular F-actin distributions of CTL as key regulators of effector function. Primary human CTL formed cell couples with tumor target cells even in the absence of antigen. Yet, the gradual stabilization of such cell couples was associated with increasing CTL effector function. Induction of suppression substantially destabilized CTL tumor cell couples.</p><p><strong>Conclusion: </strong>This comprehensive characterization of the phenotype of in vitro primary human CTL, including a suppressed state, should facilitate their use in basic research, the development of CTL-targeting therapeutics and the determination of their mechanism of action.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf023"},"PeriodicalIF":4.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531348","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":"High level of anti-drug antibodies is associated with shorter survival in advanced solid cancer patients treated with Immune checkpoint inhibitors.","authors":"Rui Zhao, Weihao Wang, Jingliang Wang, Yahui Wang, Liying Pan, Pancen Ran, Fang Luan, Guobin Fu","doi":"10.1093/immadv/ltaf019","DOIUrl":"10.1093/immadv/ltaf019","url":null,"abstract":"<p><strong>Background: </strong>Camrelizumab has become the first-line treatment for most patients with advanced tumors. Among advanced tumor patients undergoing camrelizumab, the majority develop immunogenicity, resulting in the production of anti-drug antibodies (ADA). The impact of ADA on the efficacy and safety of camrelizumab treatment is currently unknown.</p><p><strong>Method: </strong>Hematologic samples from 31 tumor patients treated with camrelizumab were collected to serve as an experimental cohort for ADA levels detection. Concurrently, a separate validation cohort consisting of 16 patients was established. Follow-up data on patients' OS and PFS were collected and analyzed.</p><p><strong>Results: </strong>High ADA levels (≥1200 ng/ml) after the three cycles camrelizumab treatment were linked to poorer patient outcomes, as shown by significant differences between PD and PR (<i>P</i> = 0016) and PR and SD (<i>P</i> = .0439). This trend was also present in the validation cohort (PD vs PR, <i>P</i> = .0413). More importantly, high ADA levels after the three cycles camrelizumab treatment were associated with a significant reduction in OS (<i>P</i> = .0128) and PFS (<i>P</i> = .0004), with the validation cohort reporting comparable findings (OS: <i>P</i> = .0009; PFS: <i>P</i> = .0007). Additionally, camrelizumab concentration was negatively correlated with ADA levels (experimental cohort: <i>R</i> ² = 0.3876; validation cohort: <i>R</i> ² = 0.3702). Patients had higher ADA levels after the early phase of camrelizumab treatment.</p><p><strong>Conclusion: </strong>High ADA levels were associated with shorter OS and PFS in patients after three cycles of camrelizumab therapy. Furthermore, patients had higher ADA levels after the early phase of treatment, specifically in the first three cycles with camrelizumab. It found that the higher the ADA concentration, the lower the serum camrelizumab concentration.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf019"},"PeriodicalIF":4.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303845","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":"Comparing DC subsets in solid tumors: what about DC3s?","authors":"Casper J Pachocki, Marianne Boes, Alsya J Affandi","doi":"10.1093/immadv/ltaf021","DOIUrl":"10.1093/immadv/ltaf021","url":null,"abstract":"<p><p>Dendritic cells (DCs) are critical sentinels of the immune system, serving as indispensable bridges between innate and adaptive immune responses. DCs are a heterogeneous population, with subsets playing specialized roles in immune defense, tolerance, or disease development. Among these, the recently redefined DC3 subset has gained attention for its unique features and potential roles in health and disease. This review focuses on the phenotypic, functional, and developmental diversity of DC subsets-primarily DC3s-and their contributions to cancer. The tumor microenvironment (TME) in solid tumors is characterized by varying degrees of immune cell infiltration, including DCs. Within the TME, DCs play diverse roles, either promoting anti-tumor responses or facilitating immune evasion. Key subsets include conventional type 1 and type 2 DCs (cDC1s and cDC2s), as well as plasmacytoid DCs (pDCs). DC3s share certain features with cDC2s and monocytes but are distinct in their phenotype, function, and ontogeny. Functionally, DC3s can prime and activate T cells, skewing CD4⁺ T cells towards Th17 and stimulating CD8⁺ T cells with a tissue-resident memory phenotype. In cancer, their presence correlates with diverse outcomes depending on the TME: DC3 presence is linked to increased survival in patients with pancreatic ductal adenocarcinoma and oropharyngeal cancer while in non-small-cell lung cancer and melanoma it is associated with immunosuppression. The emerging understanding of DC3s highlights the complexity of DC biology and its relevance to diseases. The dynamic immunomodulatory functions of DC3s open new avenues for developing targeted therapies against cancer and immune-mediated disorders.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf021"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531347","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":"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}