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

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.

Tumor microenvironment and immune surveillance

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.

Biochemical mechanisms implemented by human acute myeloid leukemia cells to suppress host immune surveillance

Acute myeloid leukaemia(AML)is a blood/bone marrow cancer originating from myeloid cell precusors capable of self-renewing.AML cells implement biochemical mechanisms which allow them not only to survive,but also to successfully escape immune surveillance.ln this work,we discuss crucial molecular mechanisms used by human AML cells in order to evade immune attack.

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

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.

Insights into the protective role of immunity in neurodegenerative disease

The immune system（IS）is set to provide protection against pathogens,surveillance against tumor cells and promotion of healing.Such functions can be efficiently performed thanks to the presence of a large network of cells with variable degrees of specialization.

Multiple characteristic alterations and available therapeutic strategies of cellular senescence

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.

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

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.

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

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.

From filaments to function: The role of the plant actin cytoskeleton in pathogen perception,signaling and immunity

The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.