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Acquired aplastic anemia:Is bystander insult to autologous hematopoiesis driven by immune surveillance against malignant cells?

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World Journal of Stem Cells 2020年第11期12卷 1429-1438页

作者： Xi-Chen Zhao Xiao-Yun Sun Bo Ju Fan-Jun Meng Hong-Guo Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.

关键词： Acquired aplastic anemia Bystander insult Malignant clonal hematopoiesis immune surveillance Antineoplastic Gut inflammation

Tumor microenvironment and immune surveillance

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Microenvironment & Microecology Research 2022年第1期4卷 28-30页

作者： Aamir Ahmad Translational Research Institute Academic Health SystemHamad Medical CorporationDoha 3050Qatar Dermatology Institute Academic Health SystemHamad Medical CorporationDoha 3050Qatar Department of Dermatology and Venereology Rumailah HospitalHamad Medical CorporationDoha 3050Qatar

Tumor microenvironment(TME)comprises of tumor cells in vicinity of many additional cell types.Among many components of TME,immune cells represent a class of distinct cells that normally would be expected to suppress tumor growth and kill tumor cells,but are,instead,modulated by tumor cells to create conditions that support tumor growth,angiogenesis,metastasis and resistance against therapies.These immune cells include lymphocytes,natural killer cells,macrophages,dendritic cells,myeloid-derived suppressor cells and regulatory T-cells.Given the role these immune cells play in immune suppression within TME,it is important to clearly understand the mechanisms thereof so that the future immunotherapies can be tweaked and many of these immune cells could be reprogrammed to perform their normal cytotoxic/phagocytic activity for elimination of tumors.

关键词： tumor microenvironment immune cells immunosuppression immune surveillance

Multiple characteristic alterations and available therapeutic strategies of cellular senescence

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第2期24卷 101-114页

作者： YUNZI ZHAO HUI LI QINGLONG GUO HUI HUI State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionChina Pharmaceutical UniversityNanjing 210009China

Given its state of stable proliferative inhibition,cellular senescence is primarily depicted as a critical mechanism by which organisms delay the progression of carcinogenesis.Cells undergoing senescence are often associated with the alteration of a series of specific features and functions,such as metabolic shifts,stemness induction,and microenvironment remodeling.However,recent research has revealed more complexity associated with senescence,including adverse effects on both physiological and pathological processes.How organisms evade these harmful consequences and survive has become an urgent research issue.Several therapeutic strategies targeting senescence,including senolytics,senomorphics,immunotherapy,and function restoration,have achieved initial success in certain scenarios.In this review,we describe in detail the characteristic changes associated with cellular senescence and summarize currently available countermeasures.

关键词： Senescence Metabolism Stemness Microenvironment Senolytic immune surveillance

Hepatitis B Virus Down-Regulates Expressions of MHC Class I Molecules on Hepatoplastoma Cell Line

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Cellular & Molecular Immunology 2006年第5期3卷 373-378页

作者： Yongyan Chen Min Cheng Zhigang Tian Institute of Immunology School of Life Sciences University of Science and Technology of China Hefei 230027 China Institute of Immunology School of Life Sciences University of Science and Technology of China 443 Huangshan Road Hefei City Anhui 230027 China

Chronic HBV infection is associated with a 100-fold high risk of developing hepatocellular carcinoma. Tumor recognition is of the most importance during the immune surveillance process that prevents cancer development in humans. In the present study, the expressions of MHC class Ⅰ molecules on hepatoplastoma cell line HepG2.2.15 were investigated to indicate the possible effects of HBV on the immune recognition during HBV-associated hepatocellular carcinoma. It was found that the expressions of MHC class Ⅰ molecules HLA-ABC, HLA-E and MICA were much lower in HepG2.2.15 cells compared with HepG2 cells. The expressing HBV in human hepatoplastoma cell line significantly down-regulated the expressions of MHC class Ⅰ molecules. Additionally, it was observed that in murine chronic HBsAg carriers the expression of classical MHC-I molecule on hepatocytes was down-regulated. These results demonstrated that HBV might affect the immune recognition during HBV- associated hepatocellular carcinoma such as the recognition of CD8^＋ T, NK-CTL and NK cells and prevent the immune surveillance against tumors. However, the effects of HBV down-regulation of MHC class I molecules on the target cells in vivo should be further studied. Cellular ＆ Molecular Immunology.

关键词： hepatitis B virus MHC hepatoplastoma cell line immune surveillance

Current Understanding on the Immunological Functions of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

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Cellular & Molecular Immunology 2005年第4期2卷 265-269页

作者： Wei Wei Yanxin Liu Dexian Zheng National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences ＆ Peking Union Medical Sciences Beijing 100005 China

Tumor necrosis factor （TNF）-related apoptosis-inducing ligand （TRAIL） selectively induces apoptosis in various tumor cells and virus-infected cells, but rarely in normal cells. The killing specificity of TRAIL has brought great interests to develop a novel apoptosis-based anti-tumor agent for clinical application. TRAIL is expressed in many normal tissues and cells, such as liver, brain, kidney, heart, colon, lung, and testis. However, immunological and physiological functions of TRAIL in vivo have not been understood well. In the present paper we summarized the progress in the research on immunological functions of TRAIL.

关键词： TRAIL immune surveillance autoimmune disease innate immunity

Adoptive immunotherapy for acute leukemia:New insights in chimeric antigen receptors

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World Journal of Stem Cells 2015年第7期7卷 1022-1038页

作者： Mael Heiblig Mohamed Elhamri Mauricette Michallet Xavier Thomas Hematology Department Lyon-Sud Hospital

Relapses remain a major concern in acute leukemia. It is well known that leukemia stem cells(LSCs) hide in hematopoietic niches and escape to the immune system surveillance through the outgrowth of poorly immunogenic tumor-cell variants and the suppression of the active immune response. Despitethe introduction of new reagents and new therapeutic approaches, no treatment strategies have been able to definitively eradicate LSCs. However, recent adoptive immunotherapy in cancer is expected to revolutionize our way to fight against this disease, by redirecting the immune system in order to eliminate relapse issues. Initially described at the onset of the 90's, chimeric antigen receptors(CARs) are recombinant receptors transferred in various T cell subsets, providing specific antigens binding in a non-major histocompatibility complex restricted manner, and effective on a large variety of human leukocyte antigen-divers cell populations. Once transferred, engineered T cells act like an expanding "living drug" specifically targeting the tumor-associated antigen, and ensure long-term antitumor memory. Over the last decades, substantial improvements have been made in CARs design. CAR T cells have finally reached the clinical practice and first clinical trials have shown promising results. In acute lymphoblastic leukemia, high rate of complete and prolonged clinical responses have been observed after anti-CD19 CAR T cell therapy, with specific but manageable adverse events. In this review, our goal was to describe CAR structures and functions, and to summarize recent data regarding pre-clinical studies and clinical trials in acute leukemia.

关键词： Chimeric antigen receptors Adoptive immunotherapy Acute leukemia T cells immune surveillance

Tumor microenvironment drives NK exhaustion by disordering metabolic program

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Tumor microenvironment drives NK exhaustion by disordering m...