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Seminars in Nephrology Jan 2022Cancer remains a significant cause of morbidity and mortality in kidney transplant recipients, due to long-term immunosuppression. Salient issues to consider in... (Review)
Review
Cancer remains a significant cause of morbidity and mortality in kidney transplant recipients, due to long-term immunosuppression. Salient issues to consider in decreasing the burden of malignancy among kidney transplant recipients include pretransplant recipient evaluation, post-transplant screening and monitoring, and optimal treatment strategies for the kidney transplant recipients with cancer. In this review, we address cancer incidence and outcomes, approaches to cancer screening and monitoring pretransplant and post-transplant, as well as treatment strategies, immunosuppressive management, and multidisciplinary approaches in the kidney transplant recipients with cancer.
Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Neoplasms
PubMed: 35618396
DOI: 10.1016/j.semnephrol.2022.01.003 -
Cell Reports. Medicine Nov 2023In this issue, Pang and colleagues identify the protease legumain as a potential immunotherapy target in glioblastoma that drives tumor-associated macrophages in...
In this issue, Pang and colleagues identify the protease legumain as a potential immunotherapy target in glioblastoma that drives tumor-associated macrophages in response to hypoxia.
Topics: Humans; Glioblastoma; Cysteine Endopeptidases; Immunosuppression Therapy; Hypoxia
PubMed: 37992680
DOI: 10.1016/j.xcrm.2023.101293 -
Transplant International : Official... Aug 2015During the past 10 years, minimization strategies have been legitimately initiated to decrease the many toxicities of calcineurin inhibitors, especially nephrotoxicity... (Review)
Review
During the past 10 years, minimization strategies have been legitimately initiated to decrease the many toxicities of calcineurin inhibitors, especially nephrotoxicity which was considered to be responsible for the majority of graft losses. Even though CNI-induced nephrotoxicity is undeniable, we have learned in the past 10 years that DSAs detected with solid-phase assays are excellent prognostic biomarkers in kidney transplantation (and in other organ transplantations as well) and that chronic antibody-mediated rejection has become the leading cause of graft loss. In this review, we will focus on the immunological risks linked to various strategies aiming at decreasing CNI doses either at time of transplantation or later in the course of follow-up. Some of these interventions are associated with an increase in acute cellular rejection rates but also with an improvement in renal function. The effects on antibody-mediated rejection and occurrence of de novo donor-specific antibodies are still under-reported. We are currently missing long-term data to appreciate the influence of these minimization strategies on graft and patient survival. This then leads to a cautious attitude regarding reducing immunosuppression.
Topics: Calcineurin Inhibitors; Drug Administration Schedule; Drug Therapy, Combination; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation
PubMed: 25809144
DOI: 10.1111/tri.12570 -
Advanced Science (Weinheim,... Oct 2021The deficiency of antigen-specific T cells and the induction of various treatment-induced immunosuppressions still limits the clinical benefit of cancer immunotherapy....
The deficiency of antigen-specific T cells and the induction of various treatment-induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo-immunotherapy adjuvanted with Toll-like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and in situ vaccination effect, indoleamine 2,3-dioxygenase (IDO) is also significantly increased in the tumor microenvironment (TME) and tumor-draining lymph node (TDLN), which offsets the activated antitumor immunity. To address the treatment-induced immunosuppression, an assemblable immune modulating suspension (AIMS) containing ICD inducer (paclitaxel) and supra-adjuvant (immune booster; R848 as a TLR 7/8a, immunosuppression reliever; epacadostat as an IDO inhibitor) is suggested and shows that it increases cytotoxic T lymphocytes and relieves the IDO-related immunosuppression (TGF-β, IL-10, myeloid-derived suppressor cells, and regulatory T cells) in both TME and TDLN, by the formation of in situ depot in tumor bed as well as by the efficient migration into TDLN. Local administration of AIMS increases T cell infiltration in both local and distant tumors and significantly inhibits the metastasis of tumors to the lung. Reverting treatment-induced secondary immunosuppression and reshaping "cold tumor" into "hot tumor" by AIMS also increases the response rate of immune checkpoint blockade therapy, which promises a new nanotheranostic strategy in cancer immunotherapy.
Topics: Animals; Breast Neoplasms; Disease Models, Animal; Immunosuppression Therapy; Immunotherapy; Nanomedicine
PubMed: 34363349
DOI: 10.1002/advs.202102043 -
Frontiers in Immunology 2020Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored... (Review)
Review
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
Topics: Animals; Humans; Immunosuppression Therapy; Mesenchymal Stem Cell Transplantation; Organ Transplantation; Transplantation Tolerance
PubMed: 33643298
DOI: 10.3389/fimmu.2020.618243 -
Clinical and Experimental Immunology Aug 2017
Topics: Animals; Humans; Immunosuppression Therapy; Immunotherapy, Adoptive; T-Lymphocytes, Regulatory; Transplantation Chimera; Transplantation Immunology; Transplantation Tolerance
PubMed: 28703287
DOI: 10.1111/cei.12994 -
Journal of Hepatology Oct 2013Despite the increase in long-term survival, liver transplant recipients still exhibit higher morbidity and mortality than the general population. This is in part... (Review)
Review
Despite the increase in long-term survival, liver transplant recipients still exhibit higher morbidity and mortality than the general population. This is in part attributed to the lifelong administration of immunosuppression and its associated side effects. Several studies reported in the last decades have evaluated the impact of immunosuppression minimization in liver transplant recipients, but results have been inconsistent due to the heterogeneity of study designs and insufficient sample sizes. On the other hand, complete immunosuppression withdrawal has proven to be feasible in approximately 20% of carefully selected liver transplant recipients, especially in older patients and those with longer duration after transplantation. The long-term risks and clinical benefits of this strategy, however, also need to be clarified. As a consequence, and despite the general perception that a large proportion of liver recipients are over-immunosuppressed, it is currently not possible to derive evidence-based guidelines on how to manage long-term immunosuppression to improve clinical outcomes. Large clinical trials of drug minimization and/or withdrawal focused on clinically-relevant long-term outcomes are required. Development of personalized medicine tools and a deeper understanding of the pathogenesis of idiopathic inflammatory graft lesions will be pre-requisites to achieve these goals.
Topics: Calcineurin Inhibitors; Clinical Trials as Topic; Evidence-Based Medicine; Hepatitis C; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Lymphocyte Depletion; Mycophenolic Acid; Steroids; T-Lymphocytes; TOR Serine-Threonine Kinases
PubMed: 23578883
DOI: 10.1016/j.jhep.2013.04.003 -
American Journal of Transplantation :... Dec 2016
Topics: Immune Tolerance; Immunosuppression Therapy; Kidney Transplantation; Transplantation Tolerance
PubMed: 27467554
DOI: 10.1111/ajt.13993 -
Medicina (Kaunas, Lithuania) Mar 2023Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection...
Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection must be balanced with the adverse events associated with immunosuppressive drugs, for example infection, renal failure, and diabetes. A triple immunosuppressive combination is standard, including a steroid, a calcineurin inhibitor, and an antiproliferative compound beginning with the highest levels of immunosuppression and a subsequent tapering of the dose, usually guided by therapeutic drug monitoring and considering clinical results, bronchoscopy sampling results, and additional biomarkers such as serum viral replication or donor-specific antibodies. Balancing the net immunosuppression level required to prevent rejection without overly increasing the risk of infection and other complications during the tapering phase is not well standardized and requires repeated assessments for dose-adjustments. In our adaptive immunosuppression approach, we additionally consider results from the white blood cell counts, in particular lymphocytes and eosinophils, as biomarkers for monitoring the level of immunosuppression and additionally use them as therapeutic targets to fine-tune the immunosuppressive strategy over time. The concept and its rationale are outlined, and areas of future research mentioned.
Topics: Humans; Transplant Recipients; Immunosuppressive Agents; Immunosuppression Therapy; Biomarkers; Lung; Graft Rejection
PubMed: 36984489
DOI: 10.3390/medicina59030488 -
Clinical & Developmental Immunology 2013
Topics: Animals; Humans; Immunosuppression Therapy; Mesenchymal Stem Cell Transplantation; Neovascularization, Physiologic; Organ Transplantation; Plastic Surgery Procedures; Skin; Transplantation Chimera; Transplantation Immunology; Transplantation Tolerance; Transplantation, Homologous
PubMed: 23573113
DOI: 10.1155/2013/689071