Cancer immunology research最新文献

{"title":"A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors.","authors":"","doi":"10.1158/2326-6066.CIR-13-10-WWR","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-13-10-WWR","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"13 10","pages":"1509"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198542","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":"Antibody Mediated Inhibition of HLA/LILR Interactions Breaks Innate Immune Tolerance and Induces Antitumor Immunity.","authors":"Abir K Panda, Kannan Natarajan, Surajit Sinha, Jiansheng Jiang, Sruthi Chempati, Lisa F Boyd, Priyanka P Desai, Maja Buszko, Yong-Hee Kim, Soha Kazmi, Bryan Fisk, Martha E Teke, Carolina M Larrain, Kirsten Remmert, Andrew M Blakely, Iyadh Douagi, Jonathan M Hernandez, David H Margulies, Ethan M Shevach","doi":"10.1158/2326-6066.CIR-25-0343","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-25-0343","url":null,"abstract":"<p><p>Immune check-point blockade for the treatment of malignancies has been focused on reversing inhibitory pathways in T lymphocytes. Natural killer (NK) cells are a potent innate defense against tumors and virally infected cells, but their therapeutic manipulation for anti-cancer immunity has been inadequately explored. Considerable attention has been focused on approaches to blocking inhibitory receptors on NK and myeloid cells. Most effort has been directed to the killer immunoglobulin-like receptors (KIR) and CD94/NKG2A on NK cells. Another set of receptors with similar function in both NK cells and myeloid cells is the leukocyte immunoglobulin like receptors (LILR) that interact with a wide variety of HLA molecules. Using pan-anti-HLA mAbs that recognize a conserved epitopic region on HLA also seen by LILR, we investigated their functional effects in several models of tumor immunity. The pan-anti-HLA-mAbs blocked the binding of most LILRs, did not block killer cell immunoglobulin-like receptors (KIR) or CD94/NKG2A/C or TCR recognition. They also activated dysfunctional NK cells explanted from a variety of human cancers, and resulted in enhancement of tumor immunity in humanized mice. The mAbs also exert direct anti-tumor effects. These results suggest that activation of innate immunity via disruption of HLA/LILR interactions is a potent approach for control of both primary tumors and potentially tumor metastases.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198503","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":"Reprogramming CD8+ T-cell Branched N-Glycosylation Limits Exhaustion, Enhancing Cytotoxicity and Tumor Killing.","authors":"Catarina M Azevedo, Bingxian Xie, William G Gunn, Ronal M Peralta, Carolina S Dantas, Henrique Fernandes-Mendes, Supriya Joshi, Victoria Dean, Pedro Almeida, Drew Wilfahrt, Nuno Mendes, Julian López Portero, Carmen Poves, María Jesús Fernández-Aceñero, Ricardo Marcos-Pinto, Ângela Fernandes, Greg M Delgoffe, Salomé S Pinho","doi":"10.1158/2326-6066.CIR-25-0313","DOIUrl":"10.1158/2326-6066.CIR-25-0313","url":null,"abstract":"<p><p>T-cell therapies have transformed cancer treatment. Although surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell-mediated tumor immunity remains an area of active investigation. In this study, we show that the intratumoral T-cell glycome is altered early in human colorectal cancer, with substantial changes in branched N-glycans. We demonstrated that CD8+ T cells expressing β1,6-GlcNAc-branched N-glycans adopted an exhausted phenotype, marked by increased PD1 and Tim3 expression. CRISPR-Cas9 deletion of key branching glycosyltransferase genes revealed that Mgat5 played a prominent role in T-cell exhaustion. In culture-based assays and tumor studies, Mgat5 deletion in CD8+ T cells resulted in improved cancer cell killing. These findings prompted the assessment of whether MGAT5 deletion in anti-CD19 chimeric antigen receptor (CAR) T cells could enable this therapeutic modality in a solid tumor setting. We showed that MGAT5 knockout anti-CD19-CAR T cells inhibited the growth of CD19-transduced tumors. Together, these findings show that MGAT5-mediated branched N-glycans regulate CD8+ T-cell function in cancer and provide a strategy to enhance the antitumor activity of native and CAR T cells.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1655-1673"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871624","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: Inflammation Mediated by Gut Microbiome Promotes Immune Suppression and Lung Adenocarcinoma Progression.","authors":"Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A Jamal, Manvi Sharma, Hannah Moreno, Ashish V Damania, Matthew C Wong, Matthew C Ross, Ansam Sinjab, Tieling Zhou, Minyue Chen, Inti Tarifa Reischle, Jiping Feng, Chidera Chukwuocha, Elizabeth Tang, Camille Abaya, Jamie K Lim, Cheuk Hong Leung, Heather Y Lin, Nathaniel Deboever, Jack J Lee, Boris Sepesi, Don L Gibbons, Jennifer A Wargo, Junya Fujimoto, Linghua Wang, Joseph F Petrosino, Nadim J Ajami, Robert R Jenq, Seyed Javad Moghaddam, Tina Cascone, Kristi Hoffman, Humam Kadara","doi":"10.1158/2326-6066.CIR-25-0804","DOIUrl":"10.1158/2326-6066.CIR-25-0804","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1687"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013803","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":"Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.","authors":"Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K McKenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph","doi":"10.1158/2326-6066.CIR-24-0897","DOIUrl":"10.1158/2326-6066.CIR-24-0897","url":null,"abstract":"<p><p>There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their invasiveness, highlighting its potential as a therapeutic target. Accordingly, we designed a second-generation human ENG-targeting CAR molecule signaling through the CD28 endodomain and retrovirally transduced primary human T cells with this CAR. ENG CAR T cells exhibited strong antigen-specific cytokine release, robust proliferation, memory formation, and cytotoxic function against various sarcoma cell lines. Their cytotoxicity remained unaffected by the presence of soluble ENG or its natural ligand, bone morphogenetic protein-9. Furthermore, ENG CAR T cells disrupted multicellular tumor spheroids in vitro, overcoming tumor compactness and the stromal barrier created by cancer-associated fibroblasts, which are critical challenges in sarcoma CAR T-cell therapy. In orthotopic xenograft models of sarcomas, ENG CAR T-cell treatment resulted in control of tumor growth and metastasis, leading to survival extension. In summary, our study describes the involvement of ENG in sarcoma metastasis and validates our human ENG CAR T cells as a potential therapeutic for advanced sarcomas.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1591-1608"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759265","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":"PI3K/Akt Signaling Pathway Regulates CD155 Expression Involved in Resistance to Cancer Immunotherapy.","authors":"Katsushige Kawase, Shusuke Kawashima, Tatsuya Nishi, Takashi Inozume, Takao Morinaga, Masahito Kawazu, Toyoyuki Hanazawa, Yosuke Togashi","doi":"10.1158/2326-6066.CIR-24-0853","DOIUrl":"10.1158/2326-6066.CIR-24-0853","url":null,"abstract":"<p><p>Despite the effectiveness of anti-PD-1/PD-L1 mAbs against various cancers, resistance remains a significant issue among patients. The immunosuppressive T-cell immunoreceptor with Ig and ITIM domains/CD155 axis has emerged as a key mechanism contributing to this resistance. However, the intricacies of CD155 expression are not fully elucidated. In this study, we aimed to identify the key molecules involved in the regulation of CD155 expression and explore their role in modulating CD155 within the tumor microenvironment (TME). By using clustered regularly interspaced palindromic repeats (CRISPR) screening, we identified dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A) as one of the key regulators of CD155 expression. Subsequent inhibition of Dyrk1a through CRISPR/CRISPR-associated protein 9 technology or treatment with DYRK1A inhibitors mitigated PD-1 blockade resistance. Moreover, in certain head and neck squamous cell carcinoma cell lines, cetuximab-mediated EGF receptor blockade reduced CD155 expression by targeting downstream PI3K/Akt signaling. In patients with head and neck squamous cell carcinoma (n = 96), CD155 expression correlated with Akt phosphorylation, particularly affecting PD-1 blockade resistance in those with high CD8+ T-cell infiltration. These findings underscore the role of the PI3K/Akt signaling pathway in regulating CD155 expression, which may influence resistance to PD-1 blockade therapies in a variety of cancers, particularly those characterized by an inflamed TME. This study suggests that targeting the PI3K/Akt pathway could overcome resistance, particularly in cancers with an inflamed TME and high CD155 expression.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1640-1654"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752500","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":"High Levels of Endogenous Omega-3 Fatty Acids Promote Dendritic Cell Antigen Presentation and Improve Dendritic Cell-Based Cancer Vaccine Efficacy in Mice.","authors":"Shweta Tiwary, Kevin S Hsu, Katherine C Goldfarbmuren, Zheng Xia, Jay A Berzofsky","doi":"10.1158/2326-6066.CIR-24-0927","DOIUrl":"10.1158/2326-6066.CIR-24-0927","url":null,"abstract":"<p><p>Antigen presentation by dendritic cells (DC) is crucial in activating T cells. DCs capture, process, and present antigens to T cells, making them attractive vaccine vehicles. However, most DC cancer vaccines have had limited clinical efficacy, suggesting a need to increase their potency. We report that high levels of omega-3 fatty acids in mice significantly prolonged lifespan and reduced tumor growth and body weight loss. This effect was mediated in part by more effective DC antigen presentation. DCs derived from Tg(CAG-fat-1)Jxk/J transgenic mice expressing high omega-3 lipid levels were better vaccine vehicles than wild-type (WT) DCs in treating cancers in WT mice and in stimulating CD8+ T-cell responses in vitro and in vivo. Although no effect on the levels of expression of costimulatory molecules was detected, we discovered a marked enhancement of T-cell dwell time on DCs. We also observed that differentiating DCs from WT bone marrow in the presence of omega-3 lipids increased DC antigen presentation capacity in vitro, suggesting a potential approach to enhance DC-based cancer vaccine efficacy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1609-1622"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774729","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":"TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.","authors":"Ishwar Navin, Matthew Dysthe, Prashant S Menon, Corrine Baumgartner, Tim Sauer, Navin Varadarajan, Robin Parihar","doi":"10.1158/2326-6066.CIR-24-0919","DOIUrl":"10.1158/2326-6066.CIR-24-0919","url":null,"abstract":"<p><p>Therapies using NK cells that express chimeric antigen receptors (CAR-NK) have been successfully employed against hematologic malignancies. However, solid tumors resist CAR-NKs partly by enriching tumor microenvironments with ligands for NK cell inhibitory receptors. Although the NK inhibitory receptor T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has been implicated in impaired antitumor activity of endogenous NK cells, the consequences of TIGIT expression on engineered CAR-NKs have not been explored. To address this gap, we compared TIGIT-expressing and TIGIT-deleted human CAR-NKs targeting the GD2 solid tumor antigen in tumor immune microenvironment co-cultures and in vivo tumor immune microenvironment xenografts designed to mimic the immunosuppressive environment of solid tumors. TIGIT-deleted GD2.CAR-NKs exhibited antitumor activity, expanded, and persisted within TIGIT ligand-enriched solid tumor environments, whereas TIGIT-expressing CAR-NKs did not. Mechanistic experiments revealed that the improved tumor control resulting from TIGIT loss on CAR-NKs was not dependent on DNAM-1 activation or enhanced cytotoxic potential but rather on downregulation of cell adhesion molecules, weakened cell avidity, and reduced synapse contact duration that, in concert, improved serial killing and allowed more efficient tumor destruction. Our study highlights a noncanonical role for TIGIT in modulating CAR-NK activity that may guide strategies to overcome inhibitory NK receptors like TIGIT and improve the efficacy of CAR-NKs against solid tumors.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1576-1590"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741284","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":"SPP1+ Tumor-Associated Macrophages Drive Immunotherapy Resistance via CD8+ T-cell Dysfunction in Clear-Cell Renal Cell Carcinoma.","authors":"Wenbin Jiang, Li Liu, Ziyang Xu, Youqi Qiu, Boyu Zhang, Jiangting Cheng, Jiyan Luo, Yang Qu, Jianming Guo, Jiejie Xu","doi":"10.1158/2326-6066.CIR-24-1146","DOIUrl":"10.1158/2326-6066.CIR-24-1146","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAM) are key regulators of tumor immunity. With advances in single-cell analyses, secreted phosphoprotein 1 (SPP1)-positive TAMs have been observed across multiple tumor sites. However, their clinical relevance and phenotypic characteristics in clear-cell renal cell carcinoma (ccRCC) have not been comprehensively delineated. Using patient-level data from two in-house cohorts (n = 355), we explored the relationship between SPP1+ TAM infiltration and therapeutic response and prognosis in ccRCC. Four publicly available datasets consisting of 1,741 patients with ccRCC were included for external validation. Cytometry by time-of-flight and flow cytometry were utilized to phenotype SPP1+ TAMs and establish their impact on CD8+ T cells. Furthermore, we established an ex vivo culture system to test the potential therapeutic value of targeting SPP1 alone and in conjunction with PD-1 inhibitors in ccRCC. We found that patients with high SPP1+ TAM infiltration exhibited worse response to immunotherapy and dismal prognosis in ccRCC. SPP1+ TAMs exhibited an immunosuppressive and protumor phenotype, and were related to impaired effector function and terminal differentiation of CD8+ T cells. Blockade of SPP1 mitigated the protumor tumor microenvironment and reinvigorated CD8+ T-cell function. Combining PD-1 blockade with SPP1 blockade boosted the expansion of CD8+ T cells and enhanced antitumor efficacy. Together, these data indicate that elevated infiltration of SPP1+ TAMs is related to worse response to immunotherapy and dysfunction of CD8+ T cells in ccRCC. We conclude that SPP1 may serve as a potential therapeutic target in ccRCC.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1533-1546"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663871","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":"Targeting Myeloid Trem2 Reprograms the Immunosuppressive Niche and Potentiates Checkpoint Immunotherapy in NASH-Driven Hepatocarcinogenesis.","authors":"Ziyi Wang, Yu Zhang, Xiangdong Li, Nan Xia, Sheng Han, Liyong Pu, Xuehao Wang","doi":"10.1158/2326-6066.CIR-24-1088","DOIUrl":"10.1158/2326-6066.CIR-24-1088","url":null,"abstract":"<p><p>Macrophages expressing Trem2 play a pivotal role in promoting nonalcoholic steatohepatitis (NASH; also known as metabolic dysfunction-associated steatohepatitis) progression to hepatocellular carcinoma (HCC). Despite the widespread clinical use of anti-PD-1 immune checkpoint blockade, its therapeutic efficacy in NASH-driven HCC remains suboptimal. This study investigates the mechanisms by which NAM Trem2 influences the response of NASH-driven HCC to immunotherapy. Clinical analysis revealed that elevated Trem2 expression in NASH is positively correlated with the accumulation of neutrophil extracellular traps (NET) and infiltration of PD-1+Eomes+CD8+ T cells and regulatory T cells. Myeloid-specific knockout of Trem2 (Trem2Δmye) led to impaired macrophage reprogramming, resulting in the accumulation of proinflammatory Ly6ChiCX3CR1lo macrophages, which enhanced degradation of NETs in NASH. Trem2Δmye also disrupted TGFβ production via P-Syk-dependent efferocytosis, collectively suppressing the differentiation of PD-1+Eomes+CD8+ T cells and regulatory T cells. The efficacy of anti-PD-1 therapy in inhibiting NASH-driven HCC progression was also significantly enhanced by Trem2Δmye, primarily through the downregulation of Treg CXCR4 expression mediated by increased NET degradation. These therapeutic effects were further amplified when combined with the CXCR2 inhibitor AZD5069. Our findings identify Trem2 as a central regulator of the NASH-driven HCC immunosuppressive niche and suggest a combinatorial therapeutic strategy that targets both myeloid reprogramming and NETosis to overcome immunotherapy resistance in metabolic liver cancer progression.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1516-1532"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764627","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}