Cancer immunology research最新文献

{"title":"Tertiary lymphoid structures are associated with enhanced macrophage activation and immune checkpoint expression, and predict outcome in cervical cancer.","authors":"Laurent Gorvel, Marylou Panouillot, Marie-Sarah Rouvière, Emilien Billon, Stéphane Fattori, Jumaporn Sonongbua, Nicolas Boucherit, Amira Ben Amara, Olivia Quilichini, Samuel Granjeaud, Clara Degos, Jacques A Nunès, Xavier Carcopino, Eric Lambaudie, Anne-Sophie Chrétien, Renaud Sabatier, Marie-Caroline Dieu-Nosjean, Daniel Olive","doi":"10.1158/2326-6066.CIR-24-0979","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0979","url":null,"abstract":"<p><p>Cervical tumors are usually treated using surgery, chemotherapy, and radiotherapy, and would benefit from immunotherapies. However, the immune microenvironment in cervical cancer remains poorly described. Tertiary lymphoid structures (TLS) were recently described as markers for better immunotherapy response and overall better prognosis in cancer patients. We evaluated the cervical tumor immune microenvironment, specifically focusing on TLS, using combined high-throughput phenotyping, soluble factor concentration dosage in the TME and spatial interaction analyses. We found that TLS presence was associated with a more inflammatory soluble microenvironment, with the presence of B cells as well as more activated macrophages and dendritic cells (DCs). Furthermore, this myeloid cell activation was associated with expression of immune checkpoints, such as PD-L1 and CD40, and proximity of activated conventional type 2 DCs (DC2) to CD8+ T cells, indicating better immune interactions and tumor control. Finally, we associated TLS presence, greater B cell density, and activated DC density with improved progression-free survival, substantiating TLS presence as a potential prognostic marker. Our results provide evidence that TLS presence denotes cell activation and immunotherapy target expression.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070739","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":"A bifunctional antibody targeting PD-1 and TGF-β signaling has antitumor activity in combination with radiotherapy and attenuates radiation-induced lung injury.","authors":"Sheng Wang, Duo Xu, Yuan Wang, Yuehua Zhou, Lingyan Xiao, Fang Li, Jingyao Tu, Wan Qin, Sidan Tian, Bolong Zheng, Yihua Wang, Xiang-Lin Yuan, Yuanhui Liu, Bo Liu","doi":"10.1158/2326-6066.CIR-23-0903","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-23-0903","url":null,"abstract":"<p><p>Radio-immunotherapy has antitumor activity but also causes toxicity, which limits its clinical application. JS-201 is a dual antibody targeting PD-1 and TGF-β signaling. We investigated the antitumour effect of JS-201 combined with radiotherapy and the effect on radiation-induced lung injury (RILI). Different tumor models were established to detect the antitumor effects of the combination of JS-201 and RT, and RILI models were established to observe the effects of JS-201. Transcriptome sequencing showed that JS-201 optimized the TME by inhibiting extracellular matrix formation and angiogenesis. Combining JS-201 with radiotherapy further increased the inflammatory response and immune infiltration and showed great abscopal effects in LLC-luc models. Single-cell sequencing demonstrated that JS-201 reduced fibroblast proliferation by inhibiting the TGF-β/Smad pathway and the release of neutrophil extracellular traps mediated by ROS, thereby relieving radiation-induced pulmonary fibrosis. In conclusion, the JS-201 and radiotherapy combination enhances antitumor effects while mitigating acute and chronic RILI, and it may have potential for translational investigation as a cancer treatment strategy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058266","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":"Preclinical Development of T Cells Engineered to Express a T-Cell Antigen Coupler Targeting Claudin 18.2-Positive Solid Tumors.","authors":"Stacey X Xu, Ling Wang, Philbert Ip, Ritu R Randhawa, Tania Benatar, Suzanna L Prosser, Prabha Lal, Alima Naim Khan, Thanyashanthi Nitya-Nootan, Gargi Thakor, Heather MacGregor, Danielle L Hayes, Andrea Vucicevic, Princy Mathew, Sadhak Sengupta, Christopher W Helsen, Andreas G Bader","doi":"10.1158/2326-6066.CIR-24-0138","DOIUrl":"10.1158/2326-6066.CIR-24-0138","url":null,"abstract":"<p><p>The T-cell antigen coupler (TAC) is a chimeric receptor that facilitates tumor antigen-specific activation of T cells by co-opting the endogenous T-cell receptor complex in the absence of tonic signaling. Previous data demonstrate that the TAC affords T cells with the ability to induce durable and safe antitumor responses in preclinical models of hematologic and solid tumors. In this study, we describe the preclinical pharmacology and safety of an autologous Claudin 18.2 (CLDN18.2)-directed TAC T-cell therapy, TAC01-CLDN18.2, in preparation for a phase I/II clinical study in subjects with CLDN18.2-positive solid tumors. Following a screen of putative TAC constructs, the specificity, activity, and cytotoxicity of TAC T cells expressing the final CLDN18.2-TAC receptor were evaluated in vitro and in vivo using gastric, gastroesophageal, and pancreatic tumor models as well as human cells derived from normal tissues. CLDN18.2-specific activity and cytotoxicity of CLDN18.2-TAC T cells were observed in coculture with various 2D tumor cultures naturally expressing CLDN18.2 as well as tumor spheroids. These effects occurred in models with low antigen levels and were positively associated with increasing CLDN18.2 expression. CLDN18.2-TAC T cells effectively eradicated established tumor xenografts in mice in the absence of observed off-target or on-target/off-tumor effects, elicited durable efficacy in recursive killing and tumor rechallenge experiments, and remained unreactive in coculture with human cells representing vital organs. Thus, the data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting antitumor response in various CLDN18.2-positive solid tumor models without notable TAC-dependent toxicities, supporting the clinical development of TAC01-CLDN18.2.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"35-46"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458700","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":"Alternate MHC I Antigen Presentation Pathways Allow CD8+ T-cell Recognition and Killing of Cancer Cells in the Absence of β2M or TAP.","authors":"Freidrich M Cruz, Laura A A Orellano, Amanda Chan, Kenneth L Rock","doi":"10.1158/2326-6066.CIR-24-0320","DOIUrl":"10.1158/2326-6066.CIR-24-0320","url":null,"abstract":"<p><p>MHC I antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability, so cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain [β2 microglobulin (β2M)] or the transporter-associated with antigen processing (TAP). β2M-null cells are generally thought to lack the MHC I pathway because the MHC I heavy chain by itself lacks the proper conformation for peptide display. TAP-null cells are thought to have severely defective MHC I antigen presentation because they are incapable of supplying peptides from the cytosol to MHC I molecules in the endoplasmic reticulum (ER). However, we have found that highly reactive memory CD8+ T cells could still recognize cells that completely lacked β2M or TAP. This was at least in part because in TAP-null cells, the Sec62 component of the Sec61 translocon supported the transfer of cytosolic peptides into the ER. In β2M-negative cells, free MHC I heavy chains were able to bind peptides and assume a conformation that was sufficiently recognized by CD8+ T cells. This process required ER chaperones and the peptide-loading complex. We found that these mechanisms supported antigen presentation at a level that was sufficient for memory CD8+ T cells to kill melanoma cells both in vitro and in tumor-bearing mice. The implications for tumor immunotherapy are discussed.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"98-108"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562642","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":"Gefitinib Reverses PD-L1-Mediated Immunosuppression Induced by Long-term Glutamine Blockade in Bladder Cancer.","authors":"Guofeng Ma, Huiqing Jia, Zhiqiang Li, Xiangyan Zhang, Liping Wang, Zhilei Zhang, Yujing Xiao, Zhijuan Liang, Dan Li, Yuanbin Chen, Xintao Tian, Yonghua Wang, Ye Liang, Haitao Niu","doi":"10.1158/2326-6066.CIR-24-0039","DOIUrl":"10.1158/2326-6066.CIR-24-0039","url":null,"abstract":"<p><p>Glutamine is a major energy source for tumor cells, and blocking glutamine metabolism is being investigated as a promising strategy for cancer therapy. However, the antitumor effect of glutamine blockade in bladder cancer remains unclear, necessitating further investigation. In this study, we demonstrated that glutamine metabolism was involved in the malignant progression of bladder cancer. Treatment with the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) inhibited the growth of bladder cancer cells in vitro in several ways. In addition, we observed inhibition of tumor growth in bladder cancer-bearing mice by using JHU083, a prodrug that was designed to prevent DON-induced toxicity. However, the antitumor immune effect of T cells changed from activation to inhibition as the administrated time extended. We found that both in vitro treatment with DON and in vivo prolonged administration of JHU083 led to the upregulation of PD-L1 in bladder cancer cells. Mechanistically, glutamine blockade upregulated PD-L1 expression in bladder cancer cells by accumulating reactive oxygen species, subsequently activating the EGFR/ERK/C-Jun signaling pathway. Combination treatment of JHU083 and gefitinib reversed the upregulation of PD-L1 in bladder cancer cells induced by prolonged glutamine blockade, resulting in the alleviation of T-cell immunosuppression and a significant improvement in therapeutic outcome. These preclinical findings show promise for glutamine metabolism targeting as a viable therapeutic strategy for bladder cancer, with the potential for further enhancement through combined treatment with gefitinib.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"66-83"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521079","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":"A Phase I Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer.","authors":"Brandon M Huffman, Osama E Rahma, Kevin Tyan, Yvonne Y Li, Anita Giobbie-Hurder, Benjamin L Schlechter, Bruno Bockorny, Michael P Manos, Andrew D Cherniack, Joanna Baginska, Adrián Mariño-Enríquez, Katrina Z Kao, Anna K Maloney, Allison Ferro, Sarah Kelland, Kimmie Ng, Harshabad Singh, Emma L Welsh, Kathleen L Pfaff, Marios Giannakis, Scott J Rodig, F Stephen Hodi, James M Cleary","doi":"10.1158/2326-6066.CIR-23-1027","DOIUrl":"10.1158/2326-6066.CIR-23-1027","url":null,"abstract":"<p><p>Ovarian cancers and microsatellite stable (MSS) colorectal cancers are insensitive to anti-programmed cell death 1 (PD-1) immunotherapy, and new immunotherapeutic approaches are needed. Preclinical data suggest a relationship between immunotherapy resistance and elevated angiopoietin 2 levels. We performed a phase I dose escalation study of pembrolizumab and the angiopoietin 1/2 inhibitor trebananib (NCT03239145). This multicenter trial enrolled patients with metastatic ovarian cancer or MSS colorectal cancer. Trebananib was administered intravenously weekly for 12 weeks with 200 mg intravenous pembrolizumab every 3 weeks. The toxicity profile of this combination was manageable, and the protocol-defined highest dose level (trebananib 30 mg/kg weekly plus pembrolizumab 200 mg every 3 weeks) was declared the maximum tolerated dose. The objective response rate for all patients was 7.3% (90% confidence interval, 2.5%-15.9%). Three patients with MSS colorectal cancer had durable responses for ≥3 years. One responding patient's colorectal cancer harbored a POLE mutation. The other two responding patients had left-sided colorectal cancers, with no baseline liver metastases, and genomic analysis revealed that they both had KRAS wild-type, ERBB2-amplified tumors. After development of acquired resistance, biopsy of one patient's KRAS wild-type ERBB2-amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD-1 immunotherapy combinations.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"9-22"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342192","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":"Level of Expression of MHCI-Presented Neoepitopes Influences Tumor Rejection by Neoantigen-Specific CD8+ T Cells.","authors":"Li Deng, Scott R Walsh, Andrew Nguyen, Jordon M Inkol, Michael J Westerveld, Lan Chen, Nader El-Sayes, Karen L Mossman, Samuel T Workenhe, Yonghong Wan","doi":"10.1158/2326-6066.CIR-23-0639","DOIUrl":"10.1158/2326-6066.CIR-23-0639","url":null,"abstract":"<p><p>Neoantigen-targeted therapy holds an array of benefits for cancer immunotherapy, but the identification of peptide targets with tumor rejection capacity remains a limitation. To better define the criteria dictating tumor rejection potential, we examined the capacity of high-magnitude T-cell responses induced toward several distinct neoantigen targets to regress MC38 tumors. Despite their demonstrated immunogenicity, vaccine-induced T-cell responses were unable to regress established MC38 tumors or prevent tumor engraftment in a prophylactic setting. Although unable to kill tumor cells, T cells showed robust killing capacity toward neoantigen peptide-loaded cells. Tumor-cell killing was rescued by saturation of target peptide-loaded MHCs on the cell surface. Overall, this study demonstrates a pivotal role for target protein expression levels in modulating the tumor rejection capacity of neoantigens. Thus, inclusion of this metric, in addition to immunogenicity analysis, may benefit antigen prediction techniques to ensure the full antitumor effect of cancer vaccines.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"84-97"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388319","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":"Deleting Trim33 in Myeloid Cells Improves the Efficiency of Radiotherapy through an IFNβ-Dependent Antitumor Immune Response.","authors":"Anaïs Assouvie, Marine Gerbé-de-Thoré, Claire Torres, Véronique Ménard, Alexia Alfaro, Eric Deutsch, Michele Mondini, Germain Rousselet","doi":"10.1158/2326-6066.CIR-24-0026","DOIUrl":"10.1158/2326-6066.CIR-24-0026","url":null,"abstract":"<p><p>Radiotherapy (RT) triggers an immune response that contributes to antitumor effects. Induction of IFNβ is a key event in this immunogenicity of RT. We have previously shown that TRIM33, a chromatin reader, restrains IFNβ expression in Toll-like receptor-activated myeloid cells. In this study, we explored whether deleting Trim33 in myeloid cells might improve the radio-induced immune response and subsequent efficiency of RT. We first established that Trim33-/- bone marrow-derived macrophages showed increased expression of IFNβ in response to direct irradiation, or to treatment with irradiated cancer cells, further supporting our hypothesis. We then tested the efficiency of a single-dose RT in three subcutaneous tumor models and one orthotopic tumor model. In all models, myeloid deletion of Trim33 led to a significantly improved response after RT, leading to a complete and durable response in most of the treated mice bearing orthotopic oral tumors. This effect required the involvement of the type I IFN pathway and the presence of CD8+ T lymphocytes but not NK cells. In addition, cured mice were capable of rejecting a secondary tumor challenge, demonstrating an in situ vaccination effect. We conclude that deleting Trim33 in myeloid cells improves RT efficiency, through a mechanism involving the type I IFN pathway and the immune response. Our work suggests that myeloid Trim33 is a host factor affecting the tumor response to RT, thus representing a new potential therapeutic target for modifying RT responses.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"109-121"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342193","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":"A Sampling of Highlights from the Literature.","authors":"","doi":"10.1158/2326-6066.CIR-13-1-WWR","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-13-1-WWR","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"13 1","pages":"7"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945102","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":"CD27-Armored BCMA CAR T-cell Therapy (CBG-002) for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial.","authors":"Yang Xu, Xuzhao Zhang, Dijia Xin, Jiawei Zhang, Luyao Wang, Yili Fan, Boxiao Chen, Wen Lei, Xi Qiu, Huawei Jiang, Xibin Xiao, Liansheng Huang, Jiandong Yu, Xin Yang, Wenjun Yang, Jiangao Zhu, Wenbin Qian","doi":"10.1158/2326-6066.CIR-24-0051","DOIUrl":"10.1158/2326-6066.CIR-24-0051","url":null,"abstract":"<p><p>B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM); however, whether patients have long-term responses has yet to be established. We investigated the feasibility of CBG-002, a CD27-armored BCMA CAR T-cell therapy, to improve clinical efficacy in patients with RRMM. We present preclinical data showing the activity of CBG-002 against myeloma and results from a phase I clinical trial (NCT04706936) evaluating its safety and efficacy in patients with RRMM. The primary endpoint was safety, as assessed by grade 3 or 4 adverse events (AE). Key secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 11 patients were enrolled and received CBG-002 therapy. Nine patients developed grade 1 or 2 cytokine release syndrome (CRS), whereas no patients experienced grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome. Other grade 3 or higher AEs included neutropenia (72.7%), thrombocytopenia (45.5%), and anemia (36.4%). At a median follow-up of 16.7 months, the ORR was 81.8%, including a stringent complete response/complete response rate of 45.5%, very good partial response rate of 18.2%, and partial response rate of 18.2%, with a median DOR of 8.9 (range 1.8-21.9) months. The median OS was not reached, and the median PFS was 8.5 (2.7-22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T-cell therapy, demonstrated safety and clinical efficacy in patients with RRMM.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"23-34"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458699","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}