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Correlation between gut microbiota and tumor immune microenvironment:A bibliometric and visualized study

World Journal of Clinical Oncology 2025年第2期16卷 110-129页

作者： Zheng-Jun Hu Hui-Rong Zhu Yong-Jie Jin Pan Liu Xiao-Wei Yu Yu-Ren Zhang Department of Oncology Shanghai Jiading District Hospital of Traditional Chinese MedicineShanghai 200000China Department of Oncology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200000China School of Chinese Medicine Anhui University of Traditional Chinese MedicineHefei 230000Anhui ProvinceChina

BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric *** To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this *** We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection *** then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in *** country with the highest number of publications was China,followed by the United *** has the highest number of citations in *** a centrality perspective,the United States has the highest influence in this *** institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang ***,the institution with the most citations was the United States National Cancer *** authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this *** most cited author was Fan *** results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in *** three most frequently used keywords were gut microbiota,tumor microenvironment,and *** This study systematically elaborates on the research progress re

关键词： Gut microbiota tumor immune microenvironment Bibliometric CiteSpace VOSviewer R-bibliometrics

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Reprogramming the tumor immune microenvironment via nanomaterial-mediated dynamic therapy

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Nano Research 2023年第12期16卷 13100-13112页

作者： Wangbo Jiao Yao Feng Chen Liang Qiaoyi Lu Haiming Fan Xing-Jie Liang Xiaoli Liu Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education College of Chemistry and Materials ScienceNorthwest UniversityXi’an 710069China Laboratory of Controllable Nanopharmaceuticals Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China Institute of Regenerative and Reconstructive Medicine Med-X InstituteFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710049China

Our improved knowledge of tumor immunology laid a solid foundation for the clinical use of tumor immunotherapies such as immune checkpoint blockers,and the efficacy of these drugs increased our confidence that immunomodulation was a viable way of treating *** basis of immunotherapy is to break the immune escape of the tumor and resolve the immune suppressive microenvironment of ***-mediated dynamic therapy(NDT)is an emerging immuno-regulatable type for tumor therapy,whose effects are mediated by increased cellular levels of reactive oxygen species(ROS).ROS is a potent trigger of immunogenic cell death,and this process initiates antitumor *** for use in NDT can be engineered to interact with almost all cell types in the tumor microenvironment to remodel this *** this review,we systematically examined the effects of NDT on four major cell types in the tumor microenvironment,namely tumor cells,lymphocytes,myeloid cells,and tumor stromal *** believe that this review will improve researchers’understanding of the anti-tumor immunity triggered by NDT,and provide ideas and inspiration for how optimally designed NDT schemes can be used to target the cells in the tumor microenvironment.

关键词： tumor immunotherapy tumor immune microenvironment nanomaterials reactive oxygen species immune cells

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Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2592-2608页

作者： Di Zhu Yu Lu Lin Gui Wenjing Wang Xi Hu Su Chen Yanming Wang Yuji Wang Department of Medicinal Chemistry College of Pharmaceutical Sciences of Capital Medical UniversityBeijing 100069China Beijing Area Major Laboratory of Peptide and Small Molecular Drugs Engineering Research Center of Endogenous Prophylactic of Ministry of Education of ChinaBeijing Laboratory of Biomedical MaterialsBeijing 100069China Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Quantum Design China Ltd. Universal Business ParkBeijing 100015China Laboratory of Biomaterials and Biomechanics Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionSchool of StomatologyCapital Medical UniversityBeijing 100050China School of Life Sciences Henan UniversityKaifeng 475004China

Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention(EPR) effect without introduction of inactive substances,and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4(PAD4) molecular inhibitor, ZD-E-1 M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps(NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pHresponsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed,while IFN-γ and TNF-a as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.

关键词： pH-Response Self-assembly Carrier-free Nanoflowers Neutrophil extracellular traps Single-cell mass cytometry tumor immune microenvironment Lymphocyte activation gene-3

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Remodeling “cold” tumor immune microenvironment via epigenetic-based therapy using targeted liposomes with in situ formed albumin corona

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Acta Pharmaceutica Sinica B 2022年第4期12卷 2057-2073页

作者： Yang He Yuefei Fang Meng Zhang Yuge Zhao Bin Tu Mingjie Shi Bahtiyor Muhitdinov Akmal Asrorov Qin Xu Yongzhuo Huang State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Zhongshan Institute for Drug Discovery Chinese Academy of SciencesZhongshan 528437China Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Artemisinin Research Center Guangzhou University of Chinese MedicineGuangzhou 510450China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310006China Institute of Bioorganic Chemistry Uzbekistan Academy of SciencesTashkent 100125Uzbekistan National Medical Products Administration Key Laboratory for Quality Research and Evaluation of Pharmaceutical ExcipientsShanghai 201203China

There is a close connection between epigenetic regulation,cancer metabolism,and *** combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer *** an epigenetic regulator of histone acetylation,panobinostat can induce histone acetylation and inhibit tumor cell proliferation,as well as regulate aerobic glycolysis and reprogram intratumoral immune ***1 is a BRD4 inhibitor that can suppress PD-L1 ***,we proposed a chemo-free,epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer.A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 *** was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin *** lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells(e.g.,tumor-associated macrophages).The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune ***,lactic acid production was reduced and angiogenesis inhibited;TAM switched to an anti-tumor phenotype,and the anti-tumor function of the effector CD8+T cells was *** strategy provides a potential method for remodeling the tumor immune microenvironment(TIME).

关键词： tumor immune microenvironment tumor-associated macrophage Epigenetic therapy immune checkpoint Angiogenesis Panobinostat JQ1 Liposome

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A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2263-2280页

作者： Leilei Wang Shanshan He Rong Liu Yuan Xue Yuan Quan Rongying Shi Xueying Yang Qing Lin Xun Sun Zhirong Zhang Ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Chemotherapeutics can induce immunogenic cell death(ICD)in tumor cells,offering new possibilities for cancer ***,the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment(TME).Here,we developed a pH/reactive oxygen species(ROS)dual-response system to enhance chemoimmunotherapy for *** system productively accumulated in tumors by specific binding of phenylboronic acid(PBA)to sialic acids(SA).The nanoparticles(NPs)rapidly swelled and released quercetin(QUE)and doxorubicin(DOX)upon the stimulation of tumor microenvironment(TME).The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice,significantly enhancing the effects of the *** study revealed DOX was an ICD inducer,stimulating immune responses and promoting maturation of dendritic cells(DCs).Additionally,QUE served as a TME regulator by inhibiting the cyclooxygenase-2(COX2)-prostaglandin E2(PGE2)axis,which influenced various immune cells,including increasing cytotoxic T cells(CLTs)infiltration,promoting M1 macrophage polarization,and reducing regulatory T cells(Tregs)*** combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive *** work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

关键词： Quercetin Nanoparticle Responsiveness Chemoimmunotherapy tumor immune microenvironment

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Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma:Relation to the immune cycle

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World Journal of Gastroenterology 2021年第31期27卷 5259-5271页

作者： Artem Mashukov Dmytro Shapochka Oleksii Seleznov Nazarii Kobyliak Tetyana Falalyeyeva Stanislav Kirkilevsky Roman Yarema Oksana Sulaieva Department of Oncology Odessa National Medical UniversityOdessa 65082Ukraine Department of Molecular Pathology and Genetics Medical Laboratory CSDKyiv 03022Ukraine Department of Pathology Medical Laboratory CSDKyiv 03022Ukraine Department of Endocrinology Bogomolets National Medical UniversityKyiv 01601Ukraine Biomedicine Educational-Scientific Center"Institute of Biology and Medicine"Taras Shevchenko National University of KyivKyiv 01601Ukraine Department of Thoracic tumors National Cancer InstituteKyiv 03022Ukraine Department of Oncology and Medical Radiology Danylo Halytsky Lviv National Medical UniversityLviv 79010Ukraine

BACKGROUND Various histological types of gastric carcinomas(GCs)differ in terms of their pathogenesis and their preexisting background,both of which could impact the tumor immune microenvironment(TIME).However,the current understanding of the immune contexture of GC is far from *** To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle *** In total,50 GC cases were examined(15 cases of diffuse GC,31 patients with intestinal-type GC and 4 cases of mucinous GC).The immunophenotype of GC was assessed and classified as immune desert(ID),immune excluded(IE)or inflamed(Inf)according to CD8+cell count and spatial *** addition,CD68+and CD163+macrophages and programmed death-ligand 1(PD-L1)expression were *** We found that GCs with different histological differentiation demonstrated distinct immune *** intestinal-type GCs had inflamed TIMEs rich in both CD8+cells and *** contrast,more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+lymphocytes but abundant CD68+macrophages,while mucinous GC had an IE-TIME with a prevalence of CD68+macrophages and CD8+lymphocytes in the peritumor ***-L1 expression prevailed mostly in intestinal-type Inf-GC,with numerous CD163+cells ***,GCs of different histological patterns have specific mechanisms of immune *** intestinal-type GC was more often related to PD-L1 expression,diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor *** These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

关键词： Gastric carcinoma tumor immune microenvironment tumor infiltrating lymphocytes tumor associated macrophages

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M6A RNA methylation modification and tumor immune microenvironment in lung adenocarcinoma

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Biophysics Reports 2023年第3期9卷 146-158页

作者： Shujuan Li Qianzhong Li Luqiang Zhang Yechen Qi Hui Bai Laboratory of Theoretical Biophysics School of Physical Science and Technology Inner Mongolia University The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock Inner Mongolia University

Lung adenocarcinoma is one of the deadliest tumors. Studies have shown that N6-methyladenosine RNA methylation regulators, as a dynamic chemical modification, affect the occurrence and development of lung adenocarcinoma. To investigate the relationship between mutations and expression levels of m6A regulators in lung adenocarcinoma, we investigated the mutations and expression levels of38 m6A regulators. We found that mutations in m6A regulatory factors did not affect the changes in expression levels, and 19 differentially expressed genes were identified. All tumor samples were classified into two subtypes based on the expression levels of 19 differentially expressed m6A-regulated genes. Survival analysis showed significant differences in survival between the two subtypes. To explore the relationship between immune cell infiltration and survival in both subtypes, we calculated the infiltration of 23 immune cells in both subtypes, and we found that the subtype with high immune cell infiltration had better survival. We found that subtypes with low tumor purity and high stromal and immune scores had better survival. The m6A-related immune genes were identified by taking the intersection of differentially expressed genes and immune genes in the two isoforms and calculating the Pearson correlation coefficients between the intersecting immune genes and the differentially expressed m6A-regulated genes. Finally, a prognostic model associated with m6A and associated with immunity was developed using prognostic genes screened from m6A-associated immune genes. The predictive power of the model was evaluated and our model was able to achieve good prediction.

关键词： Consensus clustering Lung adenocarcinoma tumor immune microenvironment M6A RNA methylation regulators immune cell infiltrates

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A Noninvasive Approach to Evaluate tumor immune microenvironment and Predict Outcomes in Hepatocellular Carcinoma

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Phenomics 2023年第6期3卷 549-564页

作者： Jianmin Wu Wanmin Liu Xinyao Qiu Jing Li Kairong Song Siyun Shen Lei Huo Lu Chen Mingshuang Xu Hongyang Wang Ningyang Jia Lei Chen Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China The International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China National Center for Liver Cancer Shanghai 201805China Department of Radiology Tongji HospitalSchool of MedicineTongji UniversityShanghai 200333China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Radiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Radiology Third Afliated Hospital of Naval Medical UniversityShanghai 200438China

It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic *** several noninvasive strategies have emerged for cancer diagnosis and prognosis,there are still lack of efective radiomic-based model to evaluate TIME status,let alone predict clinical outcome and immune checkpoint inhibitor(ICIs)response for hepatocellular carcinoma(HCC).In this study,we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response.A total of 301 patients who underwent magnetic resonance imaging(MRI)examinations were enrolled in our *** intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing(CODEX)technology,and we construct Immunoscore(IS)with the least absolute shrinkage and selection operator(LASSO)algorithm and Cox regression method to evaluate *** 6115 features extracted from MRI,fve core features were fltered out,and the Radiomic Immunoscore(RIS)showed high accuracy in predicting TIME status in testing cohort(area under the curve=0.753).More importantly,RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1(PD-1)immunotherapy in an independent cohort with advanced HCC patients(area under the curve=0.731).In comparison with previously radiomicbased models,our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding signifcance to HCC immunotherapy.

关键词： Hepatocellular carcinoma tumor immune microenvironment Radiomic Prognosis Immunotherapy response

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Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma

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中南大学学报（医学版） 2024年第5期49卷 758-774页

作者： WANG Dong DENG Qing PENG Yi TONG Zhaochen LI Zixin HUANG Liping ZENG Jin LI Jinsong MIAO Jinglei CHEN Shijie Department of Spine Surgery Third Xiangya HospitalCentral South UniversityChangsha 410013 Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor ***-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary ***,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune *** study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of ***:Anoikis-related genes(ANRGs)were obtained from *** information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)*** highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)*** learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO ***,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor ***:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic *** differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all Pmicroenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling ***:The prognostic model based on ANRGs and tumor microenvironment

关键词： anoikis tumor immune microenvironment bioinformatics prognosis osteosarcoma

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DNA Damage-driven Inflammatory Cytokines:Reprogramming of tumor immune microenvironment and Application of Oncotherapy

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Current Medical Science 2024年第2期44卷 261-272页

作者： Meng-jie WANG Yu XIA Qing-lei GAO Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Cancer Invasion and Metastasis(Ministry of Education) Hubei Key Laboratory of Tumor Invasion and MetastasisTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

DNA damage occurs across tumorigenesis and tumor *** intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor *** evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse *** cytokines possess multifaced functions in the anti-tumor immune ***,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor *** manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these *** also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

关键词： DNA damage tumor immune microenvironment inflammatory cytokines cancer therapy

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