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Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification

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International Journal of Oral Science 2024年第3期16卷 448-459页

作者： Kang Li Caihua Zhang Ruoxing Zhou Maosheng Cheng Rongsong Ling Gan Xiong Jieyi Ma Yan Zhu Shuang Chen Jie Chen Demeng Chen Liang Peng State Key Laboratory of Oncology in South China Department of Oral and Maxillofacial SurgeryInstitute of Precision MedicineCenter for Translational MedicineThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina institute for Advanced Study Shenzhen UniversityShenzhenChina Hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-Sen UniversityGuangzhouChina Senior Department of Oncology The Fifth Medical Center of PLA General HospitalBeijingChina

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is *** is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor ***,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint *** single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in *** samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised *** classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to *** found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC ***,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

关键词： prognosis elevated offering

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HBsAg stimulates NKG2D receptor expression on natural killer cellsand inhibits hepatitis C virus replication

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Hepatobiliary & Pancreatic Diseases International 2018年第3期17卷 233-240页

作者： Xiao-Xiao Wang Xiao-Ben Pan Jin-Chao Han Xu Cong Qian Jin Xiang-Sha Kong Lai Wei Bo Feng Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesNo.11 Xizhimen South StreetBeijing 100044China

Background： Higher hepatitis B surface antigen （HBsAg） facilitates hepatitis C virus （HCV） clearance inpatients with hepatitis B virus （HBV）/HCV co-infection. We investigated the effect of exogenous HBsAgon the... 详细信息

关键词： Hepatitis B surface antigen Hepatitis C virus Natural killer cells NKG2D

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cGAS-STING pathway in senescence-related inflammation

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National Science Review 2018年第3期5卷 308-310页

作者： Kun Chen Juan Liu Xuetao Cao National Key Laboratory of Medical Molecular Biology Department of Immunology & Center for Immunotherapy Institute of Basic Medical Sciences Peking Union Medical College Chinese Academy of Medical Sciences National Key Laboratory of Medical Immunology & institute of Immunology Second Military Medical University

Cellular senescence marked with persistent cell cycle arrest plays critical roles in orchestrating tissue remodeling and immune surveillance in response to multiple developmental and physiological ***,chronic or persistent cellular senescence can promote aberrant inflammatory responses,therefore is linked with variable pathogeneses such as fibrosis,cancer,autoimmune diseases,

关键词： GAS cGAS-STING pathway in senescence-related inflammation

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Programmed polymersomes with spatio-temporal delivery of antigen and dual-adjuvants for efficient dendritic cells-based cancer immunotherapy

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Chinese Chemical Letters 2022年第9期33卷 4179-4184页

作者： Hanyong Wang Xinyu Yang Chunyan Hu Chenlu Huang Hai Wang Dunwan Zhu Linhua Zhang Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China

Since antigen and adjuvant are rapid clearance in vivo,insufficient delivery to induce dendritic cells(DCs)maturation and cross-presentation,as well as limited migration efficiency of DCs to secondary lymph organs,greatly hinders the development of DCs-based ***,PCL-PEG-PCL polymersomes(PCEP-PS)as antigen and adjuvants delivery nanoplatforms(IMO-PS)were well-designed,which can electrostatically adsorb OVA antigen on the surface via DOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release,incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activating synergistic immune responses via different signaling *** IMO-PS significantly improved antigen uptake,promoted DCs maturation and cytokines *** treated with IMO-PS could enhance migration into draining lymphoid nodes,and eventually induced antigen-specific CD8+and CD4+T cell responses and OVA-specific cytotoxic T lymphocyte(CTL)*** vaccination of EG7-OVA tumor-bearing mice by IMO-PS+DCs significantly extended tumor-free time,effectively suppressed tumor growth,and greatly extended median survival *** strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.

关键词： DCs vaccine immunotherapy Imiquimod MPLA DOTAP OVA

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Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

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World Journal of Hepatology 2024年第3期16卷 353-365页

作者： Tarana Gupta Nikhil Sai Jarpula Division of Hepatology Department of MedicinePandit Bhagwat Dayal Sharma Post Graduate Institute of Medical SciencesRohtak 124001HaryanaIndia

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality *** Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular *** recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the *** HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T *** immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher ***,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

关键词： Hepatocellular carcinoma Tumor immune microenvironment Immune checkpoint inhibitor Atezolizumab Bevacizumab Pembrolizumab

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Metabolic control of T-cell immunity via epigenetic mechanisms

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Cellular & Molecular Immunology 2018年第3期15卷 203-205页

作者： Xiaomin Zhang Juan Liu Xuetao Cao National Key Laboratory of Medical Immunology&institute of Immunology Second Military Medical UniversityShanghai200433China Department of Immunology and Center for immunotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing100005China

Metabolism has been increasingly considered to play an important role in inflammation and immunity via modulating cellular signaling and transcriptional networks.1 Dysregulation of metabolic enzymes or mediators is increasingly linked to clinical diseases,such as type I diabetes,gliomas and breast cancer.2,3 Numerous metabolic sensors,such as AMP-mediated protein kinase,mammalian target of rapamycin complex1 and hypoxia-induced factor 1α(HIF-1α),have been shown to regulate immunological responses,such as T-cell activation and macrophage polarization,via modulating the property and activity of signaling pathways.4,5 Moreover,emerging evidence suggests that intermediates from multiple metabolic pathways are important in orchestrating transcriptional and epigenetic *** interaction between metabolic and epigenetic pathways is crucial for coordinating cellular immunological events in response to extracellular stimuli,such as infection,injury and stress,leading to varied biological and pathological outcomes.

关键词： immunity epigenetic inflammation

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Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

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World Journal of Gastrointestinal Oncology 2023年第8期15卷 1349-1365页

作者： Noel E Donlon Maria Davern Andrew Sheppard Fiona O'Connell Brendan Moran Timothy S Nugent Aisling Heeran James J Phelan Anshul Bhardwaj Christine Butler Narayanasamy Ravi Claire L Donohoe Niamh Lynam-Lennon Stephen Maher John V Reynolds Joanne Lysaght Cancer Immunology and immunotherapy Group Department of SurgeryTrinity Translational Medicine Institute and Trinity St James’s Cancer InstituteTrinity College DublinSt James’s HospitalDublin D08Ireland

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer ***,inducing a purposeful synergistic response between conventional therapies and the immune system remains *** release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune ***,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells *** To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic *** We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of *** expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)*** Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in *** increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral *** with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low *** In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic *** also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

关键词： Damage associated molecular patterns HMGB1 Calreticulin Oesophageal adenocarcinoma T cells Radiation

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Spatio-temporal delivery of both intra-and extracellular toll-like receptor agonists for enhancing antigen-specific immune responses

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4486-4500页

作者： Nannan Wang Yueyue Zuo Shengjie Wu Chenlu Huang Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

For cancer immunotherapy,triggering toll-like receptors(TLRs)in dendritic cells(DCs)can potentiate antigen-based immune ***,to generate robust and long-lived immune responses,a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor ***,we fabricated lipid-polymer hybrid nanoparticles(LPNPs)to spatio-temporally deliver model antigen ovalbumin(OVA)on the surface of the lipid layer,TLR4 agonist monophosphoryl lipid A(MPLA)within the lipid layer,and TLR7 agonist imiquimod(IMQ)in the polymer core to synergistically activate DCs by both extra-and intra-cellular TLRs for enhancing adaptive immune ***-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of−2.36 mV,showed a high OVA loading(around 70.83μg/mg)and IMQ encapsulation efficiency(88.04%).Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization,thereby promoting DCs maturation and cytokines *** to Free OVA,OVA-LPNPs promoted antigen uptake,lysosome escape,depot effect and migration to secondary lymphatic *** vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune ***,prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival ***,the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses,which provides a promising strategy for cancer immunotherapy.

关键词： Lipid-polymer hybrid nanoparticles TLR agonist combinations Ovalbumin Monophosphoryl lipid AImiquimod Nanovaccine Spatio-temporal manner Cancer immunotherapy

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pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy

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Acta Pharmaceutica Sinica B 2021年第2期11卷 520-533页

作者： Zhiming Zhangy Chenlu Huangy Li Zhang Qing Guo Yu Qin Fan Fan Boxuan Li Bao Xiao Dunwan Zhu Linhua Zhang Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Chemotherapy has been a major option in clinic treatment of malignant ***,single chemotherapy faces some drawbacks,such as multidrug resistance,severe side effects,which hinder its clinic application in tumor *** nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination *** the current study,a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system(denoted as M(a)D@PI-PEG-RGD)was *** bicarbonate(NH4 HCO3;abc)and chemotherapeutic agent doxorubicin(DOX)were loaded into the pores of mesoporous *** green(ICG)as a photothermal and photodynamic agent was loaded onto the polydopamine(PDA)layer *** synthesized nanoparticles displayed a narrow polydispersity(PDI)and small particle size as characterized through dynamic light scattering-autosizer *** nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal *** release analysis confirmed that the nanoparticles were pH-dependent and that NH4 HCO3 accelerated drug *** the same time,the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth *** summary,the multifunctional nanoparticles presented a promising system for combination therapy.

关键词： Mesoporous silica pH-sensitive Bubble-generating Targeting modification Combination therapy

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LHRH/TAT dual peptides-conjugated polymeric vesicles for PTT enhanced chemotherapy to overcome hepatocellular carcinoma

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Chinese Chemical Letters 2020年第12期31卷 3121-3126页

作者： Yu Qin Qing Guo Shengjie Wu Chenlu Huang Zhiming Zhang Li Zhang Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer ***,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer *** avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric *** results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination ***,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.

关键词： Redox-responsive Polymeric vesicles Chemotherapy Photothermal therapy Combination therapy

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