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Gut and Liver Jul 2016
Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Postoperative Period; Steroids; Time
PubMed: 27377738
DOI: 10.5009/gnl16204 -
Blood Nov 2022
Topics: Humans; Hemophilia A; Immunosuppression Therapy
PubMed: 36326794
DOI: 10.1182/blood.2022017947 -
Frontiers in Immunology 2018Decades of sepsis research into a specific immune system-targeting adjunctive therapy have not resulted in the discovery of an effective compound. Apart from... (Review)
Review
Decades of sepsis research into a specific immune system-targeting adjunctive therapy have not resulted in the discovery of an effective compound. Apart from antibiotics, source control, resuscitation and organ support, not a single adjunctive treatment is used in current clinical practice. The inability to determine the prevailing immunological phenotype of patients and the related large heterogeneity of study populations are regarded by many as the most important factors behind the disappointing results of past clinical trials. While the therapeutic focus has long been on immunosuppressive strategies, increased appreciation of the importance of sepsis-induced immunoparalysis in causing morbidity and mortality in sepsis patients has resulted in a paradigm shift in the sepsis research field towards strategies aimed at enhancing the immune response. However, similar to immunosuppressive therapies, precision medicine is imperative for future trials with immunostimulatory compounds to succeed. As such, identifying those patients with a severely suppressed or hyperactive immune system who will most likely benefit from either immunostimulatory or immunosuppressive therapy, and accurate monitoring of both the immune and treatment response is crucial. This review provides an overview of the challenges lying ahead on the path towards precision immunotherapy for patients suffering from sepsis.
Topics: Anti-Bacterial Agents; Humans; Immunosuppression Therapy; Precision Medicine; Sepsis
PubMed: 30233566
DOI: 10.3389/fimmu.2018.01926 -
Frontiers in Immunology 2023
Topics: Humans; Acute-On-Chronic Liver Failure; Immunosuppression Therapy; Immune Tolerance
PubMed: 37662960
DOI: 10.3389/fimmu.2023.1260749 -
Cellular & Molecular Immunology Apr 2023Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment. Despite demonstrable progress, most patients fail to respond or achieve durable... (Review)
Review
Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment. Despite demonstrable progress, most patients fail to respond or achieve durable responses due to primary or acquired ICB resistance. Recently, tumor epithelial-to-mesenchymal plasticity (EMP) was identified as a critical determinant in regulating immune escape and immunotherapy resistance in cancer. In this review, we summarize the emerging role of tumor EMP in ICB resistance and the tumor-intrinsic or extrinsic mechanisms by which tumors exploit EMP to achieve immunosuppression and immune escape. We discuss strategies to modulate tumor EMP to alleviate immune resistance and to enhance the efficiency of ICB therapy. Our discussion provides new prospects to enhance the ICB response for therapeutic gain in cancer patients.
Topics: Humans; Neoplasms; Immunotherapy; Immunosuppression Therapy; Tumor Microenvironment
PubMed: 36823234
DOI: 10.1038/s41423-023-00980-8 -
Expert Review of Molecular Diagnostics Oct 2016Identification of allograft injury, including acute clinical and subclinical injury, is vital in increasing the longevity of the transplanted organ. Acute rejection,... (Review)
Review
Identification of allograft injury, including acute clinical and subclinical injury, is vital in increasing the longevity of the transplanted organ. Acute rejection, which occurs as a result of a variety of immune and non-immune factors including the infiltration of immune cells and antibodies to the donor specific epitopes, poses a significant risk to the organ. Recent years have marked an increase in the discovery of new genomic, transcriptomic, and proteomic biomarkers in molecular diagnostics, which offer better potential for personalized management of the transplanted organ by providing earlier detection of rejection episodes. Areas covered: This review was compiled from key word searches of full-text publications relevant to the field. Expert commentary: Many of the recent advancements in the molecular diagnostics of allograft injury show much promise, but before they can be fully realized further validation in larger sample sets must be conducted. Additionally, for better informed therapeutic decisions, more work must be completed to differentiate between different causes of injury. Moreover, the diagnostics field is looking at methodologies that allow for multiplexing, the ability to identify multiple targets simultaneously, in order to provide more robust biomarkers and better understanding.
Topics: Biomarkers; Disease Management; Gene Expression Profiling; Genomics; Graft Rejection; Humans; Immunosuppression Therapy; Molecular Diagnostic Techniques; Precision Medicine; Proteomics; Transplantation Immunology
PubMed: 27677432
DOI: 10.1080/14737159.2016.1239530 -
American Journal of Transplantation :... Mar 2018A higher risk for a variety of cancers is among the major complications of posttransplantation immunosuppression. In this part of a continuing series on cancers... (Review)
Review
A higher risk for a variety of cancers is among the major complications of posttransplantation immunosuppression. In this part of a continuing series on cancers posttransplantation, this review focuses on the hematologic cancers after solid organ transplantation. Posttransplantation lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non-Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms. The other hematologic cancers include leukemias and plasma cell neoplasms (multiple myeloma and plasmacytoma). Clinical features vary across malignancies and location. Preventive screening strategies have been attempted mainly for PTLDs. Treatments include the chemotherapy regimens for the specific cancers, but also include reduction of immunosuppression, rituximab, and other therapies.
Topics: Hematologic Neoplasms; Humans; Immunosuppression Therapy; Organ Transplantation; Prognosis
PubMed: 29178667
DOI: 10.1111/ajt.14603 -
Die Anaesthesiologie Nov 2023Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important... (Review)
Review
Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important to carefully monitor the graft function in the perioperative period with respect to the occurrence of a possible rejection reaction. On the other hand, the ongoing immunosuppression may have to be adapted to the perioperative requirements in terms of the active substance and the route of administration, the resulting increased risk of infection and possible side effects (e.g., myelosuppression, nephrotoxicity and impairment of wound healing) must be included in the perioperative treatment concept. Furthermore, possible persistent comorbidities of the underlying disease and physiological peculiarities as a result of the organ transplantation must be taken into account. Support can be obtained from the expertise of the respective transplantation center.
Topics: Humans; Organ Transplantation; Anesthesia; Immunosuppression Therapy
PubMed: 37874343
DOI: 10.1007/s00101-023-01332-x -
Clinical Journal of the American... Aug 2018Most glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of... (Review)
Review
Most glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.
Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Glomerulus; Randomized Controlled Trials as Topic
PubMed: 30042223
DOI: 10.2215/CJN.01920218 -
Experimental and Clinical... Mar 2022Currentimmunosuppressive treatments for kidney transplant recipients have improved graft viability at the expense of impaired immune surveillance. The tools for... (Observational Study)
Observational Study
OBJECTIVES
Currentimmunosuppressive treatments for kidney transplant recipients have improved graft viability at the expense of impaired immune surveillance. The tools for monitoring immune status in pediatric kidney transplant recipients have not been widely investigated. Better knowledge could help recognize over immunosuppression and allow implementation of individualized preventive strategies.
MATERIALS AND METHODS
This retrospective and observational study included 28 pediatric kidney transplant recipients treated at a tertiary hospital. We measured peripheral blood lymphocyte subpopulations, immunoglobulins, immunosuppressivedrug levels, and viral loads. Reference analytical values for different age ranges were used to determine immune status. We recorded overall hospitalizations due to opportunistic infections and positive viral loads posttransplant.
RESULTS
We found hypogammaglobulinemia and lymphopenia in 19% and 41% of the patients, respectively. Peripheral blood lymphocyte subpopulations were below normal limits in one-third of the sample. These parameters were not related to the current number or plasma levels of immunosuppressive drugs. During follow-up, cytomegalovirus, Epstein-Barr virus, and BK virus viremias were detected in 60.7% of the patients. Admissions due to opportunistic infections happened in 57.1%, mainly related to severe viral disease (30%) or gastrointestinal infections (26.7%). Most occurred in younger transplant recipients and during the first 2 years posttransplant (73.3%). We found no significant relation between peripheral blood lymphocyte subpopulations and hospital admissions for opportunistic infections or positive viral loads during follow-up.
CONCLUSIONS
Recurrent hospitalizations for opportunistic infections and analytical disorders in the immune system suggested that secondary immunosuppression in pediatric kidney transplant recipients was frequent. Immunosuppression was not directly related to plasma drug levels or the number of immunosuppressive drugs. Thus, immune monitoring might be helpful in combination with immunosuppressant levels to assess immunosuppression status and to establish individualized preventive measures.
Topics: Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Kidney Transplantation; Retrospective Studies; Transplant Recipients; Treatment Outcome
PubMed: 35352632
DOI: 10.6002/ect.2021.0410