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Journal of Immunology Research 2021The main basis for hydroxychloroquine (HCQ) treatment in COVID-19 is the compound's ability to inhibit viral replication . HCQ also suppresses immunity, mainly by... (Review)
Review
The main basis for hydroxychloroquine (HCQ) treatment in COVID-19 is the compound's ability to inhibit viral replication . HCQ also suppresses immunity, mainly by interference in TLR signalling, but reliable clinical data on the extent and nature of HCQ-induced immunosuppression are lacking. Here, we discuss the mechanistic basis for the use of HCQ against SARS-CoV-2 in a prophylactic setting and in a therapeutic setting, at different stages of the disease. We argue that the clinical effect of prophylactic or therapeutic HCQ treatment in COVID-19 depends on the balance between inhibition of viral replication, immunosuppression, and off-target side effects, and that the outcome is probably dependent on disease stage and disease severity. This is supported by the initial outcomes of the well-designed randomized controlled trials: so far, evidence for a beneficial effect of HCQ treatment for COVID-19 is weak and conflicting.
Topics: Antiviral Agents; Humans; Hydroxychloroquine; Immunosuppression Therapy; SARS-CoV-2; Severity of Illness Index; Signal Transduction; Treatment Outcome; Virus Replication; COVID-19 Drug Treatment
PubMed: 33763494
DOI: 10.1155/2021/6659410 -
Frontiers in Endocrinology 2023Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain...
INTRODUCTION
Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM.
METHODS
We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models.
RESULTS
In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes.
CONCLUSION
The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.
Topics: Adult; Humans; Female; Middle Aged; Male; Cohort Studies; Immunosuppressive Agents; Immunosuppression Therapy; Antilymphocyte Serum; Diabetes Mellitus
PubMed: 37929038
DOI: 10.3389/fendo.2023.1248940 -
The British Journal of Dermatology Nov 2017
Topics: Carcinoma, Squamous Cell; Humans; Immunosuppression Therapy; Keratinocytes; Organ Transplantation; Skin Neoplasms
PubMed: 29192981
DOI: 10.1111/bjd.15932 -
American Journal of Transplantation :... Jul 2016
Topics: Immunosuppression Therapy; T-Lymphocytes
PubMed: 26792650
DOI: 10.1111/ajt.13724 -
Journal of the American College of... Jun 2019
Topics: Heart Transplantation; Humans; Immunosuppression Therapy; Incidence; Neoplasms; Sirolimus
PubMed: 31146813
DOI: 10.1016/j.jacc.2019.03.472 -
Cell Communication and Signaling : CCS May 2020Efferocytosis is a physiologic phagocytic clearance of apoptotic cells, which modulates inflammatory responses and the immune environment and subsequently facilitates... (Review)
Review
Efferocytosis is a physiologic phagocytic clearance of apoptotic cells, which modulates inflammatory responses and the immune environment and subsequently facilitates immune escape of cancer cells, thus promoting tumor development and progression. Efferocytosis is an equilibrium formed by perfect coordination among "find-me", "eat-me" and "don't-eat-me" signals. These signaling pathways not only affect the proliferation, invasion, metastasis, and angiogenesis of tumor cells but also regulate adaptive responses and drug resistance to antitumor therapies. Therefore, efferocytosis-related molecules and pathways are potential targets for antitumor therapy. Besides, supplementing conventional chemotherapy, radiotherapy and other immunotherapies with efferocytosis-targeted therapy could enhance the therapeutic efficacy, reduce off-target toxicity, and promote patient outcome. Video abstract.
Topics: Animals; Apoptosis; Disease Progression; Humans; Immunosuppression Therapy; Inflammation; Neoplasms; Phagocytosis; Regulated Cell Death; Tumor Escape
PubMed: 32370748
DOI: 10.1186/s12964-020-00542-9 -
International Journal of Molecular... Jun 2023Renal transplantation is now the best treatment for end-stage renal failure. To avoid rejection and prolong graft function, organ recipients need immunosuppressive... (Review)
Review
Renal transplantation is now the best treatment for end-stage renal failure. To avoid rejection and prolong graft function, organ recipients need immunosuppressive therapy. The immunosuppressive drugs used depends on many factors, including time since transplantation (induction or maintenance), aetiology of the disease, and/or condition of the graft. Immunosuppressive treatment needs to be personalised, and hospitals and clinics have differing protocols and preparations depending on experience. Renal transplant recipient maintenance treatment is mostly based on triple-drug therapy containing calcineurin inhibitors, corticosteroids, and antiproliferative drugs. In addition to the desired effect, the use of immunosuppressive drugs carries risks of certain side effects. Therefore, new immunosuppressive drugs and immunosuppressive protocols are being sought that exert fewer side effects, which could maximise efficacy and reduce toxicity and, in this way, reduce both morbidity and mortality, as well as increase opportunities to modify individual immunosuppression for renal recipients of all ages. The aim of the current review is to describe the classes of immunosuppressive drugs and their mode of action, which are divided by induction and maintenance treatment. An additional aspect of the current review is a description of immune system activity modulation by the drugs used in renal transplant recipients. Complications associated with the use of immunosuppressive drugs and other immunosuppressive treatment options used in kidney transplant recipients have also been described.
Topics: Humans; Kidney Transplantation; Graft Rejection; Immunosuppressive Agents; Immunosuppression Therapy; Calcineurin Inhibitors
PubMed: 37373448
DOI: 10.3390/ijms241210301 -
Cellular & Molecular Immunology Feb 2017Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical... (Review)
Review
Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.
Topics: Animals; Biomedical Research; Humans; Immunomodulation; Immunosuppression Therapy; Immunosuppressive Agents; Transplantation
PubMed: 27721455
DOI: 10.1038/cmi.2016.39 -
International Journal of Surgery... Nov 2015Neural cell transplantation has long been considered as an option for the treatment of neurodegenerative disorders. To date, several patients with Parkinson's and... (Review)
Review
Neural cell transplantation has long been considered as an option for the treatment of neurodegenerative disorders. To date, several patients with Parkinson's and Huntington's diseases have been treated with human fetal-derived neurons with disparate results. However, the limited efficacy to date combined with the scarce availability of human fetal tissues and ethical concerns render this procedure inapplicable to a wide population scale. With a view to overcoming these shortcomings, transplantation of pig-derived cell precursors has been proposed and applied in preclinical and clinical trials. Recently long-term survival (more than 18 months) associated with clinical efficacy has been reported following transplantation of genetically engineered porcine neural precursors in fully immunosuppressed primate recipients. Despite the promising results obtained to date, several questions remain unanswered. In particular, the ideal xenogeneic cell-products to transplant, the extent of the immune response against the implanted xenograft and the most suitable therapeutic strategies to improve engraftment are all issues that still need to be thoroughly addressed. The present review describes the current knowledge in the pig-to-primate xenotransplantation field. In this context, recent data on human-to-nonhuman primate xenogeneic stem cell-based treatments for neurological disorders are discussed.
Topics: Animals; Humans; Immunosuppression Therapy; Neurodegenerative Diseases; Neurons; Primates; Swine; Transplantation, Heterologous
PubMed: 26403068
DOI: 10.1016/j.ijsu.2015.09.052 -
Theranostics 2022Clinical cancer immunotherapies are usually impeded by tumor immunosuppression driven by tumor associated macrophages (TAMs). Thus, TAMs can be considered as a promising... (Review)
Review
Clinical cancer immunotherapies are usually impeded by tumor immunosuppression driven by tumor associated macrophages (TAMs). Thus, TAMs can be considered as a promising therapeutic target for improved immunotherapy, and TAMs-focused molecular targeting agents have made ideal progress in clinical practice. Even so, most TAMs-targeting agents still cannot cover up their own shortcomings as free drugs. The emergence of multifunctional nanomaterials can expectedly endow these therapeutic cargoes with high solubility, favorable pharmacokinetic distribution, cell-specific delivery, and controlled release. Here, the underlying mechanisms of tumor immunosuppression caused by TAMs are first emphatically elucidated, and then the basic design of TAMs-focused immune-nanomedicines are discussed, mainly including diverse categories of nanomaterials, targeted and stimulus-responsive modifications, and TAM imaging in nanomedicines. A summary of current TAMs-targeting immunotherapeutic mechanisms based on functional nanomedicines for TAMs elimination and/or repolarization is further presented. Lastly, some severe challenges related to functional nanomedicines for TAMs-focused cancer immunotherapy are proposed, and some feasible perspectives on clinical translation of TAMs-associated anticancer immunonanomedicines are provided. It is hoped that, with rapid development of nanomedicine in cancer immunotherapy, TAMs-focused therapeutic strategies may be anticipated to become an emerging immunotherapeutic modality for future clinical cancer treatment.
Topics: Nanomedicine; Tumor-Associated Macrophages; Immunotherapy; Immunosuppression Therapy; Nanostructures; Neoplasms
PubMed: 36451865
DOI: 10.7150/thno.78572