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Neoadjuvant and Adjuvant Therapy in Intrahepatic Cholangiocarcinoma

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Journal of clinical and Translational Hepatology 2022年第3期10卷 553-563页

作者： Xing Chen Jinpeng Du Jiwei Huang Yong Zeng Kefei Yuan department of Liver Surgery and Liver Transplantation Laboratory of Liver SurgeryState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduSichuanChina

Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the *** the incidence of ICC is relatively low,an upward trend has been seen over the past few *** to the lack of specific manifestations and tools for early diagnosis,most ICC patients have relatively advanced disease at ***,neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver ***,even after radical resection,the recurrence rate is relatively high and is a main cause leading to death after surgery,which makes adjuvant therapy *** of its low incidence,studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of *** standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence,some progress has been achieved in recent *** this review,the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated,and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.

关键词： Intrahepatic cholangiocarcinoma Neoadjuvant therapy Adjuvant therapy Recurrence Liver resection Liver transplant

Ferritin as a diagnostic, differential diagnostic, and prognostic marker for immune-related adverse events

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Cancer Biology & Medicine 2021年第4期18卷 1109-1117页

作者： Weihong Zhang Yuan Meng Lin Yang Meng Shen Li Zhou Runmei Li Yang Wang Weijiao Du Yanjuan Xiong Ying Han Xinwei Zhang Liang Liu Xiubao Ren department of Immunology and biotherapy Key Laboratory of Cancer Immunology and BiotherapyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China State Key Laboratory of Experimental Hematology Peking Union Medical CollegeInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical SciencesTianjin 300020China

Objective:Distinguishing immune-related adverse events(irAEs)caused by immune checkpoint inhibitors(ICIs)from the AEs caused by chemotherapy,targeted therapy,or infection is highly *** study offers new insights into evaluating the diagnosis,differential diagnostic,and prognostic value of ferritin for irAEs induced by ***:From December 1,2018,to April 1,2019,we examined 318 patients with malignant tumors who received serum ferritin *** cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy,and 87 patients treated with *** the 231 patients,90 had irAEs(irAE group),70 had non-irAEs(non-irAE group),67 had no AEs(no irAE-non irAE group),and 4 had unclassified *** the 87 patients,60 had AEs(AE group),and 27 had no AEs(no AE group).Statistical analyses were conducted with nonparametric Mann-Whitney ***:At the onset of AEs in the irAE group,ferritin(normal range,35–150μg/L)rose to a median of 927μg/L(range,117–17,825μg/L)from 86μg/L at baseline(range,29–421μg/L)(P<0.001).Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group(median,81μg/L;range,32–478μg/L)(P<0.001)and the AE group(median,103μg/L;range,23–712μg/L)(P<0.001).After treatment in the irAE group,ferritin continuously decreased to a normal range in recovered patients,showed no significant changes in stable patients,and continued to rise in patients who ***:Ferritin can be used as a diagnostic,differential diagnostic,and prognostic marker for irAEs in patients treated with ICIs.

关键词： Ferritin diagnosis prognosis irAEs PD-1 chemotherapy

Establishing guidelines for CAR-T cells： challenges and considerations

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Science China(Life Sciences) 2016年第4期59卷 333-339页

作者： Wei Wang Di-Yuan Qin Bing-Lan Zhang Wei Wei Yong-Sheng Wang Yu-Quan Wei State Key Laboratory of biotherapy/Collaborative Innovation center for biotherapy West China Hospital Sichuan University Chengdu 610041 China department of Emergency West China Hospital Sichuan University Chengdu 610041 China

T cells, genetically modified by chimeric antigen receptors(CAR-T), are endowed with specificity to a desired antigen and are cytotoxic to cells expressing the targeted antigen. CAR-T-based cancer immunotherapy is a promising therapy for curing hematological malignancy, such as acute lymphoid leukemia, and is promising for extending their efficacy to defeat solid tumors. To date, dozens of different CAR-T cells have been evaluated in clinical trials to treat tumors; this necessitates the establishment of guidelines for the production and application of CAR-T cells. However, it is challenging to standardize CAR-T cancer therapy because it involves a combination of gene therapy and cell therapy. In this review, we compare the existing guidelines for CAR-T cells and discuss the challenges and considerations for establishing guidance for CAR-T-based cancer immunotherapy.

关键词： chimeric antigen receptor CAR-T cells guideline cancer immunotherapy

Neoantigens:promising targets for cancer therapy

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Signal Transduction and Targeted Therapy 2023年第2期8卷 446-483页

作者： Na Xie Guobo Shen Wei Gao Zhao Huang Canhua Huang Li Fu State Key Laboratory of biotherapy and Cancer center West China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu610041China clinical Genetics Laboratory Affiliated Hospital&Clinical Medical College of Chengdu UniversityChengdu610081China Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Pharmacology and International Cancer CenterShenzhen University Health Science CenterShenzhen518060GuangdongPeople’s Republic of China

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies,including cancer vaccines,adoptive cell therapy and antibody-based therapies,especially for solid *** are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations,such as genomic mutation,dysregulated RNA splicing,disordered post-translational modification,and integrated viral open reading *** are recognized as non-self and trigger an immune response that is not subject to central and peripheral *** quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic *** to tumor-associated antigens,the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies,and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade *** development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based *** review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on *** also explore their current status,inherent challenges,and clinical translation potential.

关键词： antigens alterations approval

Maternally inherited H4K16 acetylation primes zygotic gene activation in Drosophila

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Science China(Life Sciences) 2020年第12期63卷 1950-1952页

作者： Lei Qiu Xueqin Liu Junhong Han Research Laboratory of Tumor Epigenetics and Genomics Department of General SurgeryFrontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer Centerand National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China department of clinical Research Management West China HospitalSichuan UniversityChengdu 610041China

In a recent study published in Cell, Samata et al. demonstrated a novel mechanism that guided the genomic reprogramming. They showed that the acetylation of histone H4 at Lysine 16(H4K16ac) was intergenerationally maintained from the mother’s oocyte to the young embryo and primed zygotic gene activation in Drosophila(Samata et al., 2020).Embryonic development is initially directed by maternal gene products. Then gradually, developmental control is handed to the zygotic genome during the maternal-to-zygotic transition(MZT).

关键词： activation maintained initially

Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2716-2725页

作者： Tian Hong Qinghua Luo Haiyun Ma Xin Wang Xinqiong Li Chongrong Shen Jie Pang Yan Wang Yuejia Chen Changbin Zhang Zhaoming Su Haohao Dong Xiaodi Tang department of Laboratory Medicine State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina Frontiers Medical center Tianfu Jincheng LaboratoryWest China HospitalSichuan UniversityChengduChina

CRISPR‒Cas7-11 is a Type Ⅲ-E CRISPR-associated nuclease that functions as a potent RNA editing ***-peptide repeat fused with Cas/HEF1-associated signal transducer(TPR-CHAT)acts as a regulatory protein that interacts with CRISPR RNA(crRNA)-bound Cas7-11 to form a CRISPR-guided caspase complex(Craspase).However,the precise modulation of Cas7-11’s nuclease activity by TPR-CHAT to enhance its utility requires further ***,we report cryo-electron microscopy(cryo-EM)structures of Desulfonema ishimotonii(Di)Cas7-11-crRNA,complexed with or without the full length or the N-terminus of *** structures unveil the molecular features of the Craspase *** analysis,combined with in vitro nuclease assay and electrophoretic mobility shift assay,reveals that DiTPR-CHAT negatively regulates the activity of DiCas7-11 by preventing target RNA from binding through the N-terminal 65 amino acids of DiTPR-CHAT(DiTPR-CHAT_(NTD)).Our work demonstrates that DiTPRCHAT_(NTD) can function as a small unit of DiCas7-11 regulator,potentially enabling safe applications to prevent overcutting and offtarget effects of the CRISPR‒Cas7-11 system.

关键词： CRISPR crRNA TPR

Lung microbiome:new insights into the pathogenesis of respiratory diseases

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Signal Transduction and Targeted Therapy 2024年第2期9卷 652-678页

作者： Ruomeng Li Jing Li Xikun Zhou department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesChinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and ManagementWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China

The lungs were long thought to be sterile until technical advances uncovered the presence of the lung microbial *** microbiome of healthy lungs is mainly derived from the upper respiratory tract(URT)microbiome but also has its own characteristic *** selection mechanisms in the lung,including clearance by coughing,pulmonary macrophages,the oscillation of respiratory cilia,and bacterial inhibition by alveolar surfactant,keep the microbiome transient and mobile,which is different from the microbiome in other *** pulmonary bacteriome has been intensively studied recently,but relatively little research has focused on the mycobiome and *** up-to-date review retrospectively summarizes the lung microbiome’s history,composition,and *** focus on the interaction of the lung microbiome with the oropharynx and gut microbiome and emphasize the role it plays in the innate and adaptive immune *** importantly,we focus on multiple respiratory diseases,including asthma,chronic obstructive pulmonary disease(COPD),fibrosis,bronchiectasis,and *** impact of the lung microbiome on coronavirus disease 2019(COVID-19)and lung cancer has also been comprehensively ***,by summarizing the therapeutic potential of the lung microbiome in lung diseases and examining the shortcomings of the field,we propose an outlook of the direction of lung microbiome research.

关键词： respiratory diseases Lung

Colorectal cancer-derived extracellular vesicles induce liver premetastatic immunosuppressive niche formation to promote tumor early liver metastasis

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1357-1360页

作者： Xuyang Yang Yaguang Zhang Yang Zhang Huifang Li Li Li Yangping Wu Xiangzheng Chen Lei Qiu Junhong Han Ziqiang Wang Colorectal Cancer center Department of General SurgeryState Key Laboratory of Biotherapy and Cancer Centerand Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041 Sichuan ProvinceChina State Key Laboratory of biotherapy and Cancer center and Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041 Sichuan ProvinceChina Core Facility Institute of Clinical PathologyDepartment of Respiratory and Critical Care Medicineand Department of Liver Surgery&Liver TransplantationState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China

Dear Editor,To date,the effect of colorectal cancer(CRC)-derived extracellular vesicles(EVs)on liver pre-metastatic niche(PMN)remain incompletely understood.1 To investigate the role of CRC-derived EVs in the remodeling of the liver PMN,we isolated EVs from CT26 cell culture *** characteristics of EVs(the morphology,size,and markers)were identified by transmission electron microscopy(TEM),Nanoparticle Tracking Analysis(NTA),and western blotting(Supplementary Fig.S1a–e).Then,BALB/c mice with an intact liver immune status were pretreated with CRCderived EVs and phosphate-buffered saline(PBS)for one month,and a liver metastasis model was established via spleen injection of tumor cells to determine whether EVs influence liver metastasis(Fig.1a).Two hours after the operation,in vivo imaging indicated that the animal model was successfully established,and the tumor fluorescence intensity in the liver was consistent between the two groups(Supplementary Fig.S2a,b).Amazingly,the liver tumor fluorescence intensity in the EVs group was significantly stronger than that in the PBS group after 24 h(Fig.1b;Supplementary Fig.S2c,d).The number of liver tumor nodules in the EVs group was also significantly higher than that in the PBS group on day 4(Fig.1c;Supplementary Fig.S2e,f).

关键词： metastasis metastatic cancer

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine

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Acta Pharmaceutica Sinica B 2023年第3期13卷 942-954页

作者： Xing Duan Yi Zhang Mengran Guo Na Fan Kepan Chen Shugang Qin Wen Xiao Qian Zheng Hai Huang Xiawei Wei Yuquan Wei Xiangrong Song department of Critical Care Medicine Department of Clinical PharmacyFrontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China West China Hospital Sichuan UniversityChengdu 610041China

The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and ***,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA *** further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier,a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate(SA).Intriguingly,the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA,which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@*** addition,we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen ***,we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E.G7-OVA tumor-bearing mice,dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor ***,we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

关键词： Negatively charged mRNA vaccine Sodium alginate Cationic liposome DOTAP Lysosomes escape Cancer Immunotherapy Toxicity