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Nature Reviews. Immunology Jun 2020Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent... (Review)
Review
Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
Topics: Adaptive Immunity; Animals; Epigenesis, Genetic; Humans; Immune System; Immune System Diseases; Immune Tolerance; Immunity, Innate; Immunologic Memory; Inflammation
PubMed: 32132681
DOI: 10.1038/s41577-020-0285-6 -
Cells Jun 2022Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to... (Review)
Review
Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to recipient cells and are involved in multiple physiopathological processes, including immunoregulation. Our pioneering study revealed that cancer cells release programmed death-ligand 1-positive exosomes into the circulation to counter antitumor immunity systemically via T cells. Tumor cell-derived exosomes (TDEs) also play an immunosuppressive role in other immunocytes, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs). Moreover, exosomes secreted by nontumor cells in the tumor microenvironments (TMEs) also exert immunosuppressive effects. This review systematically provides a summary of the immunosuppression induced by exosomes in tumor microenvironments, which modulates tumor growth, invasion, metastasis, and immunotherapeutic resistance. Additionally, therapeutic strategies targeting the molecular mechanism of exosome-mediated tumor development, which may help overcome several obstacles, such as immune tolerance in oncotherapy, are also discussed. Detailed knowledge of the specific functions of exosomes in antitumor immunity may contribute to the development of innovative treatments.
Topics: Exosomes; Humans; Immune Tolerance; Immunosuppression Therapy; Neoplasms; Tumor Microenvironment
PubMed: 35741075
DOI: 10.3390/cells11121946 -
Seminars in Cancer Biology Dec 2015Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding... (Review)
Review
Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.
Topics: Antigen Presentation; Carcinogenesis; Humans; Immune Evasion; Immune Tolerance; Neoplasms; Phytochemicals; T-Lymphocytes, Regulatory; Tumor Escape
PubMed: 25818339
DOI: 10.1016/j.semcancer.2015.03.004 -
Journal of Neuroinflammation Jan 2020Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients.... (Review)
Review
Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.
Topics: Animals; Humans; Immune Tolerance; Neuroimmunomodulation; Sepsis; Sepsis-Associated Encephalopathy
PubMed: 31924221
DOI: 10.1186/s12974-020-1701-3 -
The New England Journal of Medicine Sep 2020
Review
Topics: Antigen-Presenting Cells; Autoimmune Diseases; Autoimmunity; Humans; Immune Tolerance; Immunotherapy; Metabolic Networks and Pathways; Thymus Gland
PubMed: 32937048
DOI: 10.1056/NEJMra1911109 -
Trends in Immunology Feb 2014CD8 T cell activation and differentiation are tightly controlled, and dependent on the context in which naïve T cells encounter antigen, can either result in functional... (Review)
Review
CD8 T cell activation and differentiation are tightly controlled, and dependent on the context in which naïve T cells encounter antigen, can either result in functional memory or T cell dysfunction, including exhaustion, tolerance, anergy, or senescence. With the identification of phenotypic and functional traits shared in different settings of T cell dysfunction, distinctions between such dysfunctional states have become blurred. Here, we discuss distinct states of CD8 T cell dysfunction, with an emphasis on: (i) T cell tolerance to self-antigens (self-tolerance); (ii) T cell exhaustion during chronic infections; and (iii) tumor-induced T cell dysfunction. We highlight recent findings on cellular and molecular characteristics defining these states, cell-intrinsic regulatory mechanisms that induce and maintain them, and strategies that can lead to their reversal.
Topics: Animals; CD8-Positive T-Lymphocytes; Cell Differentiation; Clonal Anergy; Epigenesis, Genetic; Humans; Immune Tolerance; Immunologic Memory; Infections; Lymphocyte Activation; Mice; Neoplasms; Self Tolerance
PubMed: 24210163
DOI: 10.1016/j.it.2013.10.001 -
Nature Reviews. Immunology Mar 2012Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The... (Review)
Review
Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells - macrophages, dendritic cells and granulocytes - are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immunosuppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response.
Topics: Animals; Antineoplastic Agents; Humans; Immune Tolerance; Myeloid Cells; Neoplasms
PubMed: 22437938
DOI: 10.1038/nri3175 -
Cell Oct 2018Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other...
Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy proteins is LC3-associated phagocytosis (LAP), which functions in phagosome maturation and subsequent signaling events. Here, we show that impairment of LAP in the myeloid compartment, rather than canonical autophagy, induces control of tumor growth by tumor-associated macrophages (TAM) upon phagocytosis of dying tumor cells. Single-cell RNA sequencing (RNA-seq) analysis revealed that defects in LAP induce pro-inflammatory gene expression and trigger STING-mediated type I interferon responses in TAM. We found that the anti-tumor effects of LAP impairment require tumor-infiltrating T cells, dependent upon STING and the type I interferon response. Therefore, autophagy proteins in the myeloid cells of the tumor microenvironment contribute to immune suppression of T lymphocytes by effecting LAP.
Topics: Animals; Autophagy; Cell Line; Host-Pathogen Interactions; Humans; Immune Tolerance; Macrophages; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; Myeloid Cells; Phagocytosis; Phagosomes; T-Lymphocytes; Tumor Microenvironment
PubMed: 30245008
DOI: 10.1016/j.cell.2018.08.061 -
Frontiers in Immunology 2018In addition to determining biological sex, sex hormones are known to influence health and disease regulation of immune cell activities and modulation of target-organ... (Review)
Review
In addition to determining biological sex, sex hormones are known to influence health and disease regulation of immune cell activities and modulation of target-organ susceptibility to immune-mediated damage. Systemic autoimmune disorders, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis are more prevalent in females, while cancer shows the opposite pattern. Sex hormones have been repeatedly suggested to play a part in these biases. In this review, we will discuss how androgens and the expression of functional androgen receptor affect immune cells and how this may dampen or alter immune response(s) and affect autoimmune disease incidences and progression.
Topics: Androgens; Animals; Autoimmune Diseases; Autoimmunity; Female; Humans; Immune Tolerance; Male; Sex Characteristics
PubMed: 29755457
DOI: 10.3389/fimmu.2018.00794 -
Frontiers in Immunology 2020IL-10 is a regulator of inflammation and immunosuppression. IL-10 regulates a variety of immune cells to limit and stop the inflammatory response, and thus plays an... (Review)
Review
IL-10 is a regulator of inflammation and immunosuppression. IL-10 regulates a variety of immune cells to limit and stop the inflammatory response, and thus plays an important role in autoimmune diseases, inflammatory diseases and cancer. IL-10 is closely related to epigenetic modification, in which changes in DNA methylation of IL-10 gene can affect mRNA and protein levels of IL-10. In addition, changes in histone modifications, especially histone acetylation, can also lead to abnormal expression of IL-10 mRNA. At the same time, a handful of IL-10 related microRNAs (miRNAs) are found to be aberrantly expressed in multiple diseases. Besides, long non-coding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) also inhibits IL-10 expression. Here, we reviewed the epigenetic changes related to IL-10 in various diseases, as well as the regulation of IL-10 gene expression in various diseases by epigenetic modifications such as DNA methylation, histone modification, miRNA, and lncRNA.
Topics: Animals; Autoimmune Diseases; DNA Methylation; Epigenesis, Genetic; Female; Histone Code; Humans; Immune Tolerance; Inflammation; Interleukin-10; Male; MicroRNAs; RNA, Long Noncoding
PubMed: 32582189
DOI: 10.3389/fimmu.2020.01105