Journal for Immunotherapy of Cancer最新文献

{"title":"Long-term follow-up of BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma.","authors":"Chunxiang Jin, Rongrong Chen, Shan Fu, Mingming Zhang, Yuanyin Teng, Tingting Yang, Fengmei Song, Jingjing Feng, Ruimin Hong, Jiazhen Cui, Simao Huang, Huijun Xu, Yanlei Zhang, Guoqing Wei, Zhen Cai, Yok-Lam Kwong, Thomas Sau Yan Chan, Alex H Chang, He Huang, Yongxian Hu","doi":"10.1136/jitc-2024-010687","DOIUrl":"https://doi.org/10.1136/jitc-2024-010687","url":null,"abstract":"<p><strong>Background: </strong>B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell immunotherapy has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). This study presents the updated long-term outcomes from our center.</p><p><strong>Methods: </strong>Between July 30, 2018, and September 27, 2023, 141 patients with R/RMM who received BCMA CAR-T therapy were enrolled. Patients underwent conditioning chemotherapy with cyclophosphamide and fludarabine, followed by BCMA CAR-T cell infusion at a median dose of 2.36×10⁶ cells/kg. The study evaluated overall response rates, long-term efficacy, safety profiles, and their associations with clinical and disease characteristics.</p><p><strong>Results: </strong>At a median follow-up of 20.2 months, the safety profile of the therapy was manageable. Grade 3/4 cytokine release syndrome occurred in 36.2% of patients, with no cases of severe neurotoxicity reported. 1-month post-infusion, grade ≥3 anemia persisted in 39.6% of patients, while neutropenia (43.3%) and thrombocytopenia (52.2%) were observed. The objective response rate (ORR) among evaluable patients was 94.8%, with 50.7% achieving a complete response (CR). The 4-year progression-free survival and overall survival rates were 37.4% (95% CI, 29.1% to 48.1%) and 63.2% (95% CI, 54.8% to 72.8%), respectively, with survival curves showing gradual flattening over time. Patients with a history of autologous stem cell transplantation (ASCT) and those with extramedullary disease demonstrated significantly inferior efficacy and survival outcomes. Peak CAR-T cell expansion was positively correlated with ORR (p<0.001) and CR (p<0.001). Notably, patients with prior ASCT exhibited significantly lower CAR-T cell expansion compared with those without prior ASCT (p<0.001). Immunophenotypic analysis of infused CAR-T cells demonstrated impaired fitness in patients who received ASCT in the past year.</p><p><strong>Conclusions: </strong>BCMA CAR-T therapy in patients with R/RMM results in significant and sustained responses, with a manageable safety profile on a large scale. Prior ASCT and extramedullary disease represent adverse prognostic factors. Patients with a history of ASCT demonstrate limited peak CAR-T cell expansion.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.","authors":"Pooja Middha, Rohit Thummalapalli, Zoe Quandt, Karmugi Balaratnam, Eduardo Cardenas, Christina J Falcon, Princess Margaret Lung Group, Matthew A Gubens, Scott Huntsman, Khaleeq Khan, Min Li, Christine M Lovly, Devalben Patel, Luna Jia Zhan, Geoffrey Liu, Melinda C Aldrich, Adam Schoenfeld, Elad Ziv","doi":"10.1136/jitc-2024-011273","DOIUrl":"https://doi.org/10.1136/jitc-2024-011273","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors, but they also commonly cause immune-related adverse events (irAEs). The predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Given the similarities between irAEs and autoimmune diseases, we sought to investigate the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs.</p><p><strong>Methods: </strong>The Genetics of immune-related adverse events and Response to Immunotherapy (GeRI) cohort comprises 1302 patients with non-small cell lung cancer (NSCLC) who received ICI therapy between 2009 and 2022 at four academic medical centers. We used a published polygenic risk score for autoimmune diseases (PRS_AD) in the general population and validated it in the All of Us. We then assessed the association between PRS_AD and cessation of ICI therapy due to irAEs in the GeRI cohort, using cause-specific and Fine-Gray subdistribution hazard models. To further understand the differential effects of type of therapy on the association between PRS_AD and cessation of ICI due to irAEs, we conducted a stratified analysis by type of ICI therapy.</p><p><strong>Results: </strong>Using a competing risk model, we found an association between PRS_AD and ICI cessation due to irAEs (HR per SD=1.24, p=0.004). This association was particularly strong in patients who had ICI cessation due to irAEs within 3 months of therapy initiation (HR per SD=1.40, p=0.005). Individuals in the top quintile of PRS_AD had 4.8% ICI discontinuation for irAEs by 3 months, compared with 2% discontinuation by 3 months among patients in the bottom quintile (log-rank p=0.03). In addition, among patients who received combination programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors, ICI discontinuation for irAEs by 3 months occurred in 4 of the 13 patients (30.8%) with high PRS_AD genetic risk (top quintile) versus 3 of 21 patients (14.3%) with low PRS_AD genetic risk (bottom quintile).</p><p><strong>Conclusions: </strong>We demonstrate an association between a polygenic risk score for autoimmune disease and early ICI discontinuation for irAEs. Our results suggest that germline genetics may be used as an adjunctive tool for risk stratification around ICI clinical decision-making in solid tumor oncology.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: transfer learning radiomic model predicts intratumoral tertiary lymphoid structures in hepatocellular carcinoma: a multicenter study.","authors":"Pei Chen, Xuewei Wu, Shuixing Zhang","doi":"10.1136/jitc-2025-012007","DOIUrl":"https://doi.org/10.1136/jitc-2025-012007","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SITC strategic vision: prevention, premalignant immunity, host and environmental factors.","authors":"Sasha E Stanton, Kristin G Anderson, Tullia C Bruno, Christian M Capitini, Mary L Disis, Jennifer McQuade, Laszlo Radvanyi, Claire Vanpouille-Box, Jennifer Wargo, Kelly J Baines, Megan M Y Hong, Adnan Rajeh, Raymond H Kim, Phillip Awadalla, Lauren K Hughes, Saman Maleki Vareki","doi":"10.1136/jitc-2024-010419","DOIUrl":"https://doi.org/10.1136/jitc-2024-010419","url":null,"abstract":"<p><p>Cancer immunotherapy has improved the survival of a subset of patients by harnessing the power of the immune system to find and destroy malignant cells. The immune system also protects the host by destroying developing premalignant and malignant tumors. Advancing our knowledge of premalignant immunity and immune changes seen in lesions that develop into invasive cancer versus those that regress offers an exciting opportunity to leverage the immune system for immune prevention and immune interception of premalignancy. Understanding the immune environment of premalignant lesions and how chronic inflammation plays a central role in the evolution of premalignancy is essential for developing effective immunoprevention and immune interceptions. Factors such as host genomics and environmental factors that affect premalignant immunity and the outcome of advanced cancers are equally important in determining the response to immunotherapy. The broad use of antibiotics and factors such as obesity can disrupt a healthy gut microbiome and drive chronic inflammation that suppresses preventive immunity or the antitumor immune response required for successful immunotherapy in advanced cancers. Modifiable lifestyle factors such as diet, obesity, smoking, and stress should be considered in designing immune prevention and interception studies, as well as for patients who receive immunotherapy for advanced cancer treatment. Other factors, such as the overall immune health of patients and existing comorbidities, affect both premalignant immunity and response to immunotherapy and, therefore, should be considered in managing patients with or without cancer. The Society for Immunotherapy of Cancer previously developed an overarching manuscript regarding the challenges and opportunities that exist in cancer immunotherapy, and this manuscript serves as an in-depth follow-up regarding the topics of premalignant immunity, immune interception, and immunoprevention, and the impact of the host on responding to immunotherapy.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types'.","authors":"Jiawen Bu, Tong Zhu, Xudong Zhu","doi":"10.1136/jitc-2025-011943","DOIUrl":"https://doi.org/10.1136/jitc-2025-011943","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Antitumor effect of CAR-T cells targeting transmembrane tumor necrosis factor alpha combined with PD-1 mAb on breast cancersLeveraging T cell co-stimulation for enhanced therapeutic efficacy of trispecific antibodies targeting prostate cancer.","authors":"","doi":"10.1136/jitc-2021-003837corr1","DOIUrl":"https://doi.org/10.1136/jitc-2021-003837corr1","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of life, neurocognitive functioning, psychological issues, sexuality and comorbidity more than 2 years after commencing immune checkpoint inhibitor treatment.","authors":"Wellington Candido, Annemarie Cecile Eggen, Mathilde Jalving, Ingeborg Bosma, Reinate D Horinga, Kelly C van Heuvelen, T Jeroen N Hiltermann, Sjoukje Oosting, Emoke Racz, Melanie M van der Klauw, Anna K L Reyners, Janine Nuver","doi":"10.1136/jitc-2024-011168","DOIUrl":"https://doi.org/10.1136/jitc-2024-011168","url":null,"abstract":"<p><strong>Background: </strong>Increasing numbers of patients diagnosed with advanced cancer survive long-term after treatment with immune checkpoint inhibitors (ICIs). To design adequate interventions for these survivors, knowledge regarding quality of life (QOL) and its association with long-term and late effects of ICI treatment is required. Therefore, this study aimed to evaluate QOL, neurocognitive function, psychological issues, sexuality, and comorbidities in patients surviving at least 2 years after commencing ICI treatment.</p><p><strong>Methods: </strong>We performed a cross-sectional study in patients with stage III-IV melanoma, non-small cell lung cancer (NSCLC), urothelial cell carcinoma (UCC), or renal cell carcinoma (RCC) who survived at least 2 years after the start of ICIs. We assessed QOL, neurocognitive function, psychological issues, sexual function and comorbidity in survivors. Additionally, we evaluated QOL of informal caregivers.</p><p><strong>Results: </strong>132 survivors (70 melanoma, 50 NSCLC, 12 UCC or RCC) and 80 caregivers were included. Median age was 65 years (range 30-85) and 50 survivors were women (38%). Median time since start and cessation of ICI treatment was 33 (range 21-91) and 18 (range 0-68) months, respectively. Average survivor QOL was comparable to the reference population, but 37 (28%) survivors had poor QOL. Depression and anxiety were negatively correlated with all QOL domains. Although immune-related adverse events were common, there was no association with lower QOL. Caregiver and survivor QOL were only weakly related. Neurocognitive concerns and formally tested neurocognitive impairment were present in 22 (17%) and 13 (15%) survivors, respectively, and were not associated with a diagnosis of brain metastases. Men had a high prevalence of erectile dysfunction and low sexual satisfaction. Half of the survivors met the criteria for the metabolic syndrome.</p><p><strong>Conclusions: </strong>At least 2 years after the start of ICI treatment, one-quarter of cancer survivors had a clinically relevant lower QOL. This was associated with symptoms of depression and anxiety, but not with immune-related adverse events. Sexual issues and metabolic syndrome are prevalent. Survivorship care should address these issues in this population.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orlistat facilitates immunotherapy via AKT-FOXO3a-FOXM1-mediated PD-L1 suppression.","authors":"Qingyun Tang, Jie Li, Lianhua Zhang, Shuo Zeng, Qiyu Bao, Weichao Hu, Lijiao He, Guiping Huang, Liting Wang, Yunyi Liu, Xiaoyan Zhao, Shiming Yang, Changjiang Hu","doi":"10.1136/jitc-2024-008923","DOIUrl":"10.1136/jitc-2024-008923","url":null,"abstract":"<p><strong>Background: </strong>The immunotherapy targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death ligand-1 (PD-L1) has achieved significant breakthroughs, but further improvements are still needed in cancer treatment.</p><p><strong>Methods: </strong>We investigated orlistat, a drug approved by the Food and Drug Administration for the treatment of obesity and found that it can enhance the efficacy of CTLA-4 blockade immunotherapy. We conducted both in vivo and in vitro experiments to explore the mechanism by which orlistat increased antitumor immunity.</p><p><strong>Results: </strong>Orlistat enhances the efficacy of anti-CTLA-4 immunotherapy by suppressing tumor cell PD-L1 protein expression and boosting the transcription of interferon-stimulated genes (ISGs) and MHC-I. Mechanistically, orlistat inhibits AKT activity and subsequent phosphorylation of forkhead box O3a (FOXO3a) at its threonine (T) 32, serine (S) 253, thereby downregulating Forkhead box M1 (FOXM1) expression, which ultimately suppresses PD-L1 transcription. Specifically, inhibition of FOXM1 leads to FOXO3a accumulation through impaired AKT activity. FOXM1 activates protein kinase B (AKT) via acting as a scaffold to facilitate 3-phosphoinositide-dependent protein kinase 1 (PDK1) and AKT and interaction. In addition, orlistat enhances phosphorylated signal transducer and activator of transcription 1 (p-STAT1) at tyrosine (Y) 701, resulting in upregulation of ISGs and MHC-I.</p><p><strong>Conclusions: </strong>Orlistat plays a crucial role in modulating the immune response and supporting the combination with CTLA-4 blockade to promote antitumor immunotherapy.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Leveraging T cell co-stimulation for enhanced therapeutic efficacy of trispecific antibodies targeting prostate cancer.","authors":"","doi":"10.1136/jitc-2024-010140corr1","DOIUrl":"10.1136/jitc-2024-010140corr1","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment.","authors":"Wen-Ling Chen, Yong-Lin Chang, Su-Fang Lin, Ulrike Protzer, Masanori Isogawa, Hung-Chih Yang, Li-Rung Huang","doi":"10.1136/jitc-2024-009827","DOIUrl":"10.1136/jitc-2024-009827","url":null,"abstract":"<p><strong>Background: </strong>Impairment of Akt signaling has been observed in antigen-specific cytotoxic T lymphocytes (CTLs) during chronic viral infections or tumor progression. Despite numerous studies emphasizing Akt's role in driving CTL effector functions, there is limited exploration of using Akt molecules in T-cell engineering to enhance their antiviral or antitumor capabilities for therapeutic purposes. Some studies even conclude that inhibiting Akt activation during the in vitro expansion process can prevent T-cell exhaustion and boost the antitumor effector functions of chimeric antigen receptor-T cells in vivo. Given the unique expression patterns and functions of the three Akt isoforms in immune cells, we proposed that Akt isoforms in CTLs may regulate effector functions and T-cell exhaustion distinctly.</p><p><strong>Methods: </strong>In this study, we genetically modified tumor/virus-antigen-specific T-cell receptor tg CTLs to ectopically express Akt isoforms via retroviral transduction. We subsequently conducted western blotting, flow cytometry, and RNA sequencing analysis to assess their Akt expression, expression of immune checkpoints, antitumor/antivirus functionalities, and transcriptome. Additionally, we employed a persistent Hepatitis B Virus mouse model and a syngeneic hepatocellular carcinoma mouse model for further evaluation of their antivirus/antitumor efficacies.</p><p><strong>Results: </strong>We found that both Akt1 and Akt2 overexpression enhanced the cytotoxic capabilities of mouse CTLs, although with different dynamics. Specifically, Akt2 signaling in CTLs accelerated effector functions, leading to a rapid attack on tumor cells. Conversely, Akt1 signaling triggered calcium influx and subsequent nuclear factor of activated T cells (NFAT) activation, while Akt2 signaling suppressed calcium influx, preventing excessive NFAT expression and nuclear translocation. This repression of NFAT transcriptional activity by Akt2 signaling during prolonged antigen stimulation subsequently led to reduced expression of transcription factors associated with T-cell exhaustion, such as Egr2, Nr4a, Tox, and immune checkpoints. Consequently, Akt2-overexpressed CTLs displayed reduced T-cell exhaustion within the tumor microenvironment and efficiently eradicated tumors.</p><p><strong>Conclusion: </strong>These findings highlight the essential role of Akt signaling in enabling tumor-specific CTLs to eliminate cancer cells in the solid TME, with Akt isoforms differentially regulating the calcium-calcineurin-NFAT signaling pathway. This discovery suggests the potential of AKT2 in T-cell engineering technology to enhance the survival and effector functions of adoptively transferred T cells for treating liver malignancies or chronic viral infections.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}