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Eye (London, England) Nov 2020
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 32341535
DOI: 10.1038/s41433-020-0875-3 -
Oncoimmunology 2023Ferroptosis has gained interest due to it immunogenicity and the higher sensitivity of cancer cells to it. However, it was recently shown that ferroptosis in...
Ferroptosis has gained interest due to it immunogenicity and the higher sensitivity of cancer cells to it. However, it was recently shown that ferroptosis in tumor-associated neutrophils leads to immunosuppression and negatively impacts therapy. Here, we discuss the potential implications of the two sides (friend foe) of ferroptosis in cancer immunotherapy.
Topics: Ferroptosis; Immunotherapy; Immunosuppression Therapy; Neutrophils; Neoplasms
PubMed: 36875549
DOI: 10.1080/2162402X.2023.2182992 -
Cell Proliferation Nov 2019The skin is a highly complex organ, responsible for sensation, protection against the environment (pollutants, foreign proteins, infection) and thereby linked to the... (Review)
Review
The skin is a highly complex organ, responsible for sensation, protection against the environment (pollutants, foreign proteins, infection) and thereby linked to the immune and sensory systems in the neuro-immuno-cutaneous (NIC) system. Cutaneous innervation is a key part of the peripheral nervous system; therefore, the skin should be considered a sensory organ and an important part of the central nervous system, an 'active interface' and the first connection of the body to the outside world. Peripheral nerves are a complex class of neurons within these systems, subsets of functions are conducted, including mechanoreception, nociception and thermoception. Epidermal and dermal cells produce signalling factors (such as cytokines or growth factors), neurites influence skin cells (such as via neuropeptides), and peripheral nerves have a role in both early and late stages of the inflammatory response. One way this is achieved, specifically in the cutaneous system, is through neuropeptide release and signalling, especially via substance P (SP), neuropeptide Y (NPY) and nerve growth factor (NGF). Cutaneous, neuronal and immune cells play a central role in many conditions, including psoriasis, atopic dermatitis, vitiligo, UV-induced immunosuppression, herpes and lymphomas. Therefore, it is critical to understand the connections and interplay between the peripheral nervous system and the skin and immune systems, the NIC system. Relevant in vitro tissue models based on human skin equivalents can be used to gain insight and to address impact across research and clinical needs.
Topics: Animals; Epidermis; Humans; Immunosuppression Therapy; Inflammation; Neuropeptides; Skin; Tissue Engineering
PubMed: 31441145
DOI: 10.1111/cpr.12677 -
Frontiers in Immunology 2022Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension,... (Review)
Review
Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient's B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes.
Topics: Autoimmune Diseases; Clinical Studies as Topic; Graft Rejection; Humans; Immunosuppression Therapy; Organ Transplantation; T-Lymphocytes, Regulatory
PubMed: 35185868
DOI: 10.3389/fimmu.2022.746889 -
International Journal of Surgery... Nov 2015The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are... (Review)
Review
The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years.
Topics: Animals; Hepatocytes; Humans; Immunity, Innate; Immunosuppression Therapy; Liver Failure, Acute; Liver Transplantation; Swine; Transplantation, Heterologous
PubMed: 26361861
DOI: 10.1016/j.ijsu.2015.08.077 -
Clinical and Experimental Immunology Aug 2017In the 1960s, our predecessors won a historical battle against acute rejection and ensured that transplantation became a common life-saving treatment. In parallel with... (Review)
Review
In the 1960s, our predecessors won a historical battle against acute rejection and ensured that transplantation became a common life-saving treatment. In parallel with this success, or perhaps because of it, we lost the battle for long-lived transplants, being overwhelmed with chronic immune insults and the toxicities of immunosuppression. It is likely that current powerful treatments block acute rejection, but at the same time condemn the few circulating donor cells that would have been able to elicit immunoregulatory host responses towards the allograft. Under these conditions, spontaneously tolerant kidney recipients - i.e. patients who maintain allograft function in the absence of immunosuppression - are merely accidents; they are scarce, mysterious and precious. Several teams pursue the goal of finding a biomarker that would guide us towards the 'just right' level of immunosuppression that avoids rejection while leaving some space for donor immune cells. Some cellular assays are attractive because they are antigen-specific, and provide a comprehensive view of immune responses toward the graft. These seem to closely follow patient regulatory capacities. However, these tests are cumbersome, and require abundant cellular material from both donor and recipient. The latest newcomers, non-antigen-specific recipient blood transcriptomic biomarkers, offer the promise that a practicable and simple signature may be found that overcomes the complexity of a system in which an infinite number of individual cell combinations can lead possibly to graft acceptance. Biomarker studies are as much an objective - identifying tolerant patients, enabling tolerance trials - as a means to deciphering the underlying mechanisms of one of the most important current issues in transplantation.
Topics: Biomarkers; Host vs Graft Reaction; Humans; Immunosuppression Therapy; Kidney; Kidney Transplantation; Transplantation Tolerance; Transplantation, Homologous
PubMed: 28449211
DOI: 10.1111/cei.12981 -
Clinics in Laboratory Medicine Mar 2019There has been a prolific amount of research dedicated to the T-regulatory cells (Tregs) and their role in achieving immune homeostasis. Here, the authors briefly... (Review)
Review
There has been a prolific amount of research dedicated to the T-regulatory cells (Tregs) and their role in achieving immune homeostasis. Here, the authors briefly discuss the known biology, utilization, and potential of Tregs, for current trials and future immunotherapy. Most current trials of Treg therapies include either ex vivo expanded Tregs transferred into the peripheral blood of patients with diseases of immunologic origin or interleukin 2 injected to stimulate Tregs directly. Ongoing trials designed to measure the clinical efficacy and safety profile of these novel therapeutic approaches have resulted in largely favorable outcomes in a variety of autoimmune and alloimmune diseases.
Topics: Cell Transplantation; Immune Tolerance; Immunosuppression Therapy; Immunotherapy; Signal Transduction; T-Lymphocytes, Regulatory
PubMed: 30709499
DOI: 10.1016/j.cll.2018.11.001 -
Cellular Immunology Mar 2021Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of cancer, providing long-term... (Review)
Review
Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of cancer, providing long-term regressions in patients. However, only a minority of patients that receive ACT with tumor-specific T cells exhibit durable benefit. Thus, there is an urgent need to characterize mechanisms of resistance and define strategies to alleviate immunosuppression in the context of ACT in cancer. This article reviews the importance of lymphodepleting regimens in promoting the optimal engraftment and expansion of T cells in hosts after adoptive transfer. In addition, we discuss the role of concomitant immunosuppression and the accumulation of myeloid derived suppressor cells (MDSCs) during immune recovery after lymphodepleting regimens and mobilization regimens.
Topics: Adoptive Transfer; Animals; Cell- and Tissue-Based Therapy; Humans; Immune Tolerance; Immunosuppression Therapy; Immunotherapy, Adoptive; Lymphocyte Depletion; Myeloid Cells; Myeloid-Derived Suppressor Cells; Myelopoiesis; Neoplasms; T-Lymphocytes
PubMed: 33476931
DOI: 10.1016/j.cellimm.2020.104277 -
Biology of Blood and Marrow... Aug 2016Hematopoietic stem cell transplantation (HSCT) has an integral role in the treatment of malignant and nonmalignant diseases. Long-term complications after HSCT have been... (Review)
Review
Hematopoietic stem cell transplantation (HSCT) has an integral role in the treatment of malignant and nonmalignant diseases. Long-term complications after HSCT have been well established and include graft-versus-host disease (GVHD), conditioning regimen-related toxicities, disease relapse, and infections. Immune-mediated phenomena are increasingly described after HSCT with clinically significant sequelae. Diagnosis is challenging because of features that overlap with other commonly reported post-transplantation complications. Patients who experience immune-mediated disease after HSCT tend to have poor outcomes. Early recognition of immune-mediated complications is imperative to reduce preventable morbidity and mortality. This review looks at the currently available literature on pathogenesis, incidence, risk factors, treatment, and outcomes of immune-mediated disease (other than GVHD) after HSCT.
Topics: Autoimmune Diseases; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Prognosis; Risk Factors; Transplantation Immunology
PubMed: 27095688
DOI: 10.1016/j.bbmt.2016.04.005 -
Viruses Feb 2023Chicken anemia virus (CAV) and Gyrovirus homsa 1 (GyH1) are members of the Gyrovirus genus. The two viruses cause similar clinical manifestations in chickens, aplastic...
Chicken anemia virus (CAV) and Gyrovirus homsa 1 (GyH1) are members of the Gyrovirus genus. The two viruses cause similar clinical manifestations in chickens, aplastic anemia and immunosuppression. Our previous investigation displays that CAV and GyH1 often co-infect chickens. However, whether they have synergistic pathogenicity in chickens remains elusive. Here, we established a co-infection model of CAV and GyH1 in specific pathogen-free (SPF) chickens to explore the synergy between CAV and GyH1. We discovered that CAV and GyH1 significantly inhibited weight gain, increased mortality, and hindered erythropoiesis in co-infected chickens. Co-infected chickens exhibited severe immune organ atrophy and lymphocyte exhaustion. The proventriculus and gizzard had severe hemorrhagic necrosis and inflammation. We also discovered that the viral loads and shedding levels were higher and lasted longer in CAV and GyH1 co-infected chickens than in mono-infected chickens. Our results demonstrate that CAV and GyH1 synergistically promote immunosuppression, pathogenicity, and viral replication in co-infected chicken, highlighting the interaction between CAV and GyH1 in the disease process and increasing potential health risk in the poultry breeding industry, and needs further attention.
Topics: Animals; Chicken anemia virus; Gyrovirus; Chickens; Immunosuppression Therapy; Coinfection
PubMed: 36851729
DOI: 10.3390/v15020515