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Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma

Cancer Biology & Medicine 2020年第3期17卷 726-739页

作者： Liang Wang Steven Mo Xin Li Yingzhi He Jing Yang Department of Hematology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine Beihang University and Capital Medical UniversityBeijing Tongren HospitalBeijing 100730China Nanning Life-Ontology Biotechnology Co. Ltd.Nanning 530000China Department of Hematology Zhujiang Hospital of Southern Medical UniversityGuangzhou 510280China

Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence *** heterogenous cell populations contribute to relapse remains to be ***:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant *** identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell ***,we identified cell markers,including a series of genes associated with immune escape and drug *** addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL ***:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B *** drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival *** III B cells closely communicate with other *** key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic ***:This study investigated potential immune escape and drug resistance mechanisms in *** results may guide individualized treatment and promote the development of therapeutic drugs.

关键词： Cell heterogeneity immune escape mantle cell lymphoma multidrug resistance scRNA-seq

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HLA class Ⅰ loss in colorectal cancer:implications for immune escape and immunotherapy

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Cellular & Molecular Immunology 2021年第3期18卷 556-565页

作者： Per Anderson Natalia Aptsiauri Francisco Ruiz-Cabello Federico Garrido Instituto de Investigaci6n Biosanitaria(ibs.GRANADA) GranadaSpain Servicio de Analisis Clinicos e Inmunologia Hospital Universitario Virgen de las Nieves18014 GranadaSpain Departamento de Bioqufmica Bioiogta Molecular 3 e InmunologiaUniversidad de GranadaGranadaSpain

T cell-mediated immune therapies have emerged as a promising treatment modality in different malignancies including colorectal cancer(CRC).However,only a fraction of patients currently respond to *** the lack of responses and finding biomarkers with predictive value is of great *** is evidence that CRC is a heterogeneous disease and several classification systems have been proposed that are based on genomic instability,immune cell infiltration,stromal content and molecular subtypes of gene *** leukocyte antigen class Ⅰ(HLA-Ⅰ)plays a pivotal role in presenting processed antigens to T lymphocytes,including tumour *** molecules are frequently lost in different types of cancers,including CRC resulting in tumour immune escape from cytotoxic T lymphocytes during the natural history of cancer *** aim of this review is to(i)summarize the prevalence and molecular mechanisms behind HLA-Ⅰ loss in CRC,(ii)discuss HLA-Ⅰ expression/loss in the context of the newly identified CRC molecular subtypes,(iii)analyze the HLA-Ⅰ phenotypes of CRC metastases disseminated via blood or the lymphatic system,(iv)discuss strategies to recover/circumvent HLA-I expression/loss and finally(v)review the role of HLA class Ⅱ(HLA-Ⅱ)in CRC prognosis.

关键词： Colorectal cancer immune escape HLA ClassⅠ

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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell RNA-seq analysis

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Frontiers of Medicine 2024年第1期18卷 147-168页

作者： Weiwei Xian Mohammad Asad Shuai Wu Zhixin Bai Fengjiao Li Junfeng Lu Gaoyu Zu Erin Brintnell Hong Chen Ying Mao Guomin Zhou Bo Liao Jinsong Wu Edwin Wang Linya You Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghai200032China Cumming School of Medicine University of CalgaryCalgaryAlbertaT2N 4N1Canada Glioma Surgery Division Department of NeurosurgeryHuashan HospitalFudan UniversityShanghai200040China Department of Pathology Huashan HospitalFudan UniversityShanghai200040China Department of Neurosurgery Huashan HospitalFudan UniversityShanghai200040China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Fudan UniversityShanghai200040China School of Mathematics and Statistics Hainan Normal UniversityHaikou570100China

The association of neurogenesis and gliogenesis with glioma remains *** conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-OPC)-like and radial glia(RG)-like tumors and validated it in a public cohort and TCGA *** RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations,and the pri-OPC-like ones were prone to carrying TP53 *** subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes,suggesting their distinct immune evasion ***,the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct *** specific genes not expressed in normal immune cells were found in glioma-infiltrating *** example,glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes,*** expression was positively correlated with those of immune checkpoint genes(e.g.,LGALS33)and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat *** finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

关键词： single-cell RNA-seq glioma radial glia primitive oligodendrocyte precursor cell immune escape

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Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma

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World Journal of Gastroenterology 2005年第24期11卷 3719-3723页

作者： Li-NingXu Sheng-QuanZou Jian-MingWang DepartmentofGeneralSurgeryofTongjiHospital TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnologyWuhan430030HubeiProvinceChina

AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor ***: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues,18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder ***: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (x2 = 4.89, P＜0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t'= 4.19, P＜0.01) and chronic cholecystitis (t'= 8.06, P＜0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma than that in poorly-differentiated carcinoma (t'= 2.63, P＜0.05) and Nevin Ⅳ-Ⅴ carcinoma(t'= 3.33, P＜0.01). The confidence interval (CI) ofinfiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma wasvery significantly lower than that in carcinoma (t' = 6.99,P＜0.01), adenoma (t' = 3.66, P＜0.01), poorly-differentiated carcinoma (t' = 5.31, P＜0.01) and Nevin Ⅳ-Ⅴ carcinoma(t' = 3.76, P＜0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P＜0.05), and was not significantly lower in Nevin Ⅰ-Ⅲ carcinoma than in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P＞0.05).

关键词： Fas Fas ligand immune escape Gallbladder carcinoma

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SARS-CoV-2 variants,immune escape,and countermeasures

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Frontiers of Medicine 2022年第2期16卷 196-207页

作者： Yi Zhang Haocheng Zhang Wenhong Zhang Department of Infectious Diseases National Medical Center for Infectious DiseasesShanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseHuashan HospitalFudan UniversityShanghai 200040China State Key Laboratory of Genetic Engineering and Institute of Biostatistics School of Life SciencesFudan UniversityShanghai 200040China

Coronavirus disease 2019(COVID-19)has become a global pandemic ***-CoV-2 variants have aroused great concern and are expected to continue *** many countries have promoted rollout vaccination,the immune barrier has not yet been fully established,indicating that populations remain susceptible to *** this review,we summarize the literature on variants of concern and focus on the changes in their transmissibility,pathogenicity,and resistance to the immunity constructed by current ***,we analyzed relationships between variants and breakthrough infections,as well as the paradigm of new variants in countries with high vaccination *** transmission,continuing to strengthen variant surveillance,and combining nonpharmaceutical intervention measures and vaccines are necessary to control these variants.

关键词： SARS-CoV-2 COVID-19 vaccine immune escape breakthrough prevention

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Multi-target combinatory strategy to overcome tumor immune escape

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Frontiers of Medicine 2022年第2期16卷 208-215页

作者： Yingyan Yu Department of General Surgery of Ruijin Hospital Shanghai Institute of Digestive Surgeryand Shanghai Key Laboratory for Gastric NeoplasmsShanghai Jiao Tong University School of MedicineShanghai 200025China

immune therapy has become the fourth approach after surgery,chemotherapy,and radiotherapy in cancer *** immune checkpoints were identified in the last decade since ipilimumab,which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4,had been approved by the US Food and Drug Administration(FDA)for the treatment of unresectable or metastatic melanoma in *** use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the ***,fewer people are benefitting from immune checkpoint inhibitor treatment in solid *** 80%of patients do not respond appropriately because of primary or acquired therapeutic *** with the characterization of more immune checkpoints,the combinatory treatment of multi-immune checkpoint inhibitors becomes a new option when monotherapy could not receive a good *** this work,the author focuses on the combination therapy of multiple immune checkpoints(does not include targeted therapy of oncogenes or chemotherapy),introduces the current progression of multiple immune checkpoints and their related inhibitors,and discusses the advantages of combination therapy,as well as the risk of immune-related adverse events.

关键词： immune checkpoints multi-target immune escape immune-related adverse events combination therapy

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Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer

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Cancer Biology & Medicine 2021年第1期18卷 155-171页

作者： Kaiyuan Wang Jian Wang Ting Liu Wenwen Yu Nan Dong Chen Zhang Wenbin Xia Feng Wei Lili Yang Xiubao Ren Department of Anesthesiology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of Immunology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of Cancer Biobank Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of Biotherapy Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China

Objective:Patients with cancer pain are highly dependent on morphine analgesia,but studies have shown a negative correlation between morphine demand and patient *** long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide(M3G)***,the effects of M3G on tumor progression are worth ***:The effects of M3G on PD-L1 expressions in human non-small cell lung cancer(NSCLC)cell lines were first *** of TLR4 downstream pathways after M3G treatment was then determined by Western *** effects of M3G on human cytotoxic T lymphocytes(CTL)cytotoxicity and INF-γrelease was also ***,the LLC murine lung adenocarcinoma cell line were used to establish a murine lung cancer model,and the effects of M3G on tumor growth and metastasis were ***:M3G promoted the expressions of PD-L1 in the A549 and H1299 cell lines in a TLR4-dependent manner(Pimmune escape.

关键词： Non-small cell lung cancer TLR4 PD-L1 morphine-3-glucuronide immune escape

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ROS-sensitive PD-L1 siRNA cationic selenide nanogels for self-inhibition of autophagy and prevention of immune escape

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Bioactive Materials 2024年第11期41卷 597-610页

作者： Jie Gao Yonghua Zhai Weihong Lu Xianghe Jiang Jingsheng Zhou Lili Wu Longhai Du Chunqing Ou Xinyi Zhang Hanliang He Jian Zhu Zhengbiao Zhang Meiyun Li Yan Wu Xiangqiang Pan State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationCollege of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou215123China Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghai200433China Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices Shanghai200433China College of Life Science Mudanjiang Medical UniversityMudanjiang157011China Department of Orthopedics Jinshan HospitalFudan UniversityShanghai201508China The Department of Orthopedic Surgery Dushu Lake Hospital Affiliated to Soochow UniversitySuzhou215028China

In the field of cancer therapy,inhibiting autophagy has emerged as a promising ***,pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1(PD-L1),enabling tumor immune *** address this issue,we developed innovative ROS-responsive cationic poly(ethylene imine)(PEI)nanogels using selenol chemistry-mediated multicomponent reaction(MCR)*** procedure involved simple mixing of low-molecular-weight PEI(LMW PEI),γ-selenobutylacetone(γ-SBL),and poly(ethylene glycol)methacrylate(PEGMA).Through high-throughput screening,we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels,which exhibited a size of approximately 200 nm,excellent colloidal stability,and the most effective PD-L1 silencing *** nanogels demonstrated enhanced uptake by tumor cells,excellent oxidative degradation ability,and inhibited autophagy by alkalinizing *** A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I(MHC-I),resulting in robust proliferation of specific CD8+T cells and a decrease in MC38 tumor *** a result,the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy,upregulation of MHC-I,and downregulation of *** with dynamic diselenide bonds,the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

关键词： Multicomponent reaction ROS sensitive Cationic nanogel Autophagy inhibition immune escape

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Role of immune escape in different digestive tumours

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World Journal of Clinical Cases 2021年第34期9卷 10438-10450页

作者： Xin-Zhu Du Bin Wen Lin Liu Ying-Ting Wei Kui Zhao Department of Gastroenterology The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

A counterbalance between immune cells and tumour cells is key to fighting tumours,and immune escape is an important mechanism for the survival of tumour cells in the *** cells and their cytokines impair the activity of T cells,NK cells,macrophages and other immune cells through various ways,and change the expression of their own surface antigens so as to avoid the clearance of the immune *** in major histocompatibility complex molecules,high expression of programmed death-ligand 1,and the presence of immunosuppressive cells in the tumor microenvironment(TME)are main means by which tumors impair the function of immune *** the development of tumours of the digestive system,different mechanisms acting on tumour cells,the TME,and immune cells lead to immune escape and promote tumour *** this paper,the mechanisms of immune escape in tumour cells of the digestive system are reviewed to provide a theoretical basis for the immunotherapy of gastrointestinal tumours.

关键词： Gastrointestinal tumors immune escape immune cells Tumor microenvironment Molecular Mechanism

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Possible mechanisms associated with immune escape and apoptosis on anti-hepatocellular carcinoma effect of Mu Ji Fang granules

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World Journal of Gastrointestinal Oncology 2023年第3期15卷 504-522页

作者： Yi-Bing Zhang Yong-Rui Bao Shuai Wang Tian-Jiao Li He Tai Jia-Peng Leng Xin-Xin Yang Bo-Cai Wang Xian-Sheng Meng College of Pharmacy Liaoning University of Traditional Chinese MedicineDalian 116600Liaoning ProvinceChina Department of Clinical Trail Institution Office Dalian Municipal Central HospitalDalian 116033Liaoning ProvinceChina Technical Innovation Center of Multidimensional Analysis of Traditional Chinese Medicine of Liaoning Province Dalian 116600Liaoning ProvinceChina Engineering Laboratory of Modern Chinese Medicine Research of Liaoning Province Dalian 116600Liaoning ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common digestive system cancers with high mortality rates *** main ingredients in Mu Ji Fang Granules(MJF)are alkaloids,flavonoids,and *** has been used in the clinical treatment of hepatitis,cirrhosis and HCC for more than 30 *** previous studies have focused on the mechanism of MJF on tumor immunology in the treatment of *** To explore the mechanism of action of MJF on tumor immunology in the treatment of *** The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight-Mass Spectrometry,and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment *** male mice were randomly divided into the Blank,Model,and MJF groups(1.8,5.4,and 10.8 g/kg/d)following 7 d of oral *** body weight gain,spleen and thymus indices were calculated,tumor tissues were stained with hematoxylin and eosin,and Interferon gamma(IFN-γ),Tumor necrosis factorα(TNF-α),Interleukin-2,aspartate aminotransferase,alanine aminotransferase,alpha-fetoprotein(AFP),Fas,and FasL were measured by Enzyme-linked Immunosorbent *** mRNA expression of Bax and Bcl2 was evaluated by Real Time Quantitative PCR(RTqPCR)and protein expression of Transforming growth factorβ1(TGF-β1)and Mothers against decapentaplegic homolog(SMAD)4 was assessed by Western *** HepG2 cell line was treated with 10 mg/mL,20 mg/mL,30 mg/mL,40 mg/mL of MJF,and another 3 groups were treated with TGF-β1 inhibitor(LY364947)and different doses of *** mRNA expression of TNF-α,IFN-γ,Bax and Bcl2 was evaluated by RT-qPCR and protein expression of TGF-β1,SMAD2,p-SMAD2,SMAD4,and SMAD7 was assessed by Western *** It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumorbearing mice,protected immune organs and liver

关键词： Mu Ji Fang granules Hepatocellular carcinoma Transforming growth factorβ1/Mothers against decapentaplegic homolog immune escape H22 tumor-bearing mice HepG2 cells

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