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Signal Transduction and Targeted Therapy Oct 2021Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during... (Review)
Review
Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during tumor progression. These cells not only support immune escape directly but also promote tumor invasion via various non-immunological activities. Besides, this group of cells are proved to impair the efficiency of current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs are considered as potential therapeutic targets for cancer therapy. Treatment strategies targeting MDSCs have shown promising outcomes in both preclinical studies and clinical trials when administrated alone, or in combination with other anticancer therapies. In this review, we shed new light on recent advances in the biological characteristics and immunosuppressive functions of MDSCs. We also hope to propose an overview of current MDSCs-targeting therapies so as to provide new ideas for cancer treatment.
Topics: Humans; Immune Tolerance; Immunosuppressive Agents; Immunotherapy; Myeloid-Derived Suppressor Cells; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 34620838
DOI: 10.1038/s41392-021-00670-9 -
Clinical Infectious Diseases : An... Oct 2021Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for... (Review)
Review
Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual's ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Organ Transplantation
PubMed: 32803228
DOI: 10.1093/cid/ciaa1189 -
Autoimmunity Reviews Jan 2021Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Immunosuppressive treatments are part of the therapeutic armamentarium in MG. Long-term... (Review)
Review
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Immunosuppressive treatments are part of the therapeutic armamentarium in MG. Long-term systemic steroid administration carry considerable risks and adverse events. Consequently, steroid-free immunosuppressive therapy is necessary to reduce the dose or discontinue steroids. First immunosuppressive drug trials in MG were performed in the mid-60s using standard and nonspecific immunosuppression. Since then, only few randomized controlled clinical trials were conducted in MG and assesed drug efficacy in terms of its steroid-sparing capacity and the ability to reduce myasthenic signs and symptoms. Treatment strategy in MG is quite challenging, mainly due to the disease heterogeneity in terms of clinical presentation, immunopathogenesis and drug response. To solve this dilemma, emerging treatment are based on biological drugs and use new targets of the immune pathway.
Topics: Autoantibodies; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Myasthenia Gravis; Steroids
PubMed: 33197578
DOI: 10.1016/j.autrev.2020.102712 -
World Journal of Gastroenterology Oct 2020Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory... (Review)
Review
Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease (IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.
Topics: Colitis; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 33132635
DOI: 10.3748/wjg.v26.i38.5797 -
Clinics in Chest Medicine Mar 2015Diseases and therapies that reduce cell-mediated immunity increase the risk of nontuberculous mycobacterial (NTM) disease. Extrapulmonary NTM disease, including... (Review)
Review
Diseases and therapies that reduce cell-mediated immunity increase the risk of nontuberculous mycobacterial (NTM) disease. Extrapulmonary NTM disease, including disseminated, skin, and catheter-related disease, is more common in immunosuppressed than immunocompetent patients. Mycobacterium avium complex remains the most common cause of NTM infection, but rapid growers including Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum play an important role in skin and catheter-related infections. With the exception of antibiotic prophylaxis for AIDS patients, the prevention of NTM remains difficult. Management is complicated, involving restoration of immune function and removal of catheters in addition to treatment with species-specific antibiotics per current guidelines.
Topics: Anti-Bacterial Agents; Drug Administration Schedule; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung Diseases; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 25676522
DOI: 10.1016/j.ccm.2014.11.002 -
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 -
Cytokine & Growth Factor Reviews Feb 2023Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis, a complicated immune response is initiated, which varies... (Review)
Review
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis, a complicated immune response is initiated, which varies over time with sustained excessive inflammation and immunosuppression. Identifying a promising way to orchestrate sepsis-induced immunosuppression is a challenge. Myeloid-derived suppressor cells (MDSCs) comprise pathologically activated neutrophils and monocytes with potent immunosuppressive activity. They play an important part in inhibiting innate and adaptive immune responses, and have emerged as part of the immune response in sepsis. MDSCs numbers are persistently high in sepsis patients, and associated with nosocomial infections and other adverse clinical outcomes. However, their characteristics and functional mechanisms during sepsis have not been addressed fully. Our review sheds light on the features and suppressive mechanism of MDSCs. We also review the potential applications of MDSCs as biomarkers and targets for clinical treatment of sepsis.
Topics: Humans; Myeloid-Derived Suppressor Cells; Sepsis; Immunosuppression Therapy; Immune Tolerance; Monocytes
PubMed: 35927154
DOI: 10.1016/j.cytogfr.2022.07.007 -
Clinical Journal of the American... Aug 2021The long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin... (Review)
Review
The long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5-8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor-based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.
Topics: Abatacept; Adrenal Cortex Hormones; Calcineurin Inhibitors; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; MTOR Inhibitors; Maintenance Chemotherapy; Mycophenolic Acid; Tacrolimus; Time Factors
PubMed: 33853841
DOI: 10.2215/CJN.15040920 -
Transplant International : Official... Jan 2021Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic... (Review)
Review
Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.
Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Postoperative Complications; Retrospective Studies; Risk Factors
PubMed: 33135259
DOI: 10.1111/tri.13783 -
International Maritime Health 2017Given a better quality of life and extended life expectancy in patients with immune suppression, the number of immunocompromised travellers is constantly growing. The... (Review)
Review
Given a better quality of life and extended life expectancy in patients with immune suppression, the number of immunocompromised travellers is constantly growing. The aim of the article is to discuss travel-related health problems in immunocompromised patients, their most common destinations and reasons to travel, as well as complications associated with travel to regions with harsh environmental conditions. The article focuses on selected groups of immunocompromised travellers (ICTs), i.e., cancer patients, transplant patients receiving immunosuppressant agents, splenectomised patients and HIV-infected individuals. The most common infections and complications, including traveller's diarrhoea, vector-borne diseases (yellow fever, malaria, leishmaniasis, dengue, chikungunya), respiratory infections (including tuberculosis), and dermatoses were taken into account. Preventive measures dedicated to ICTs (pre-travel consultation, vaccinations, malaria chemoprophylaxis, prevention during travelling) have been also characterised.
Topics: Communicable Disease Control; HIV Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Splenectomy; Travel; Travel Medicine; Vaccination
PubMed: 29297574
DOI: 10.5603/IMH.2017.0041