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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 -
Frontiers in Immunology 2023Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet... (Review)
Review
Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the minutes, days and weeks following injury, damage associated molecular patterns (DAMPs) are a heterogeneous collection of proteins, lipids and DNA renowned for initiating the systemic inflammatory response syndrome. Suggesting additional immunomodulatory roles in the post-trauma immune response, data are emerging implicating DAMPs as potential mediators of post-trauma immune suppression. Discussing the results of and studies, the purpose of this review is to summarise the emerging immune tolerising properties of cytosolic, nuclear and mitochondrial-derived DAMPs. Direct inhibition of neutrophil antimicrobial activities, the induction of endotoxin tolerance in monocytes and macrophages, and the recruitment, activation and expansion of myeloid derived suppressor cells and regulatory T cells are examples of some of the immune suppressive properties assigned to DAMPs so far. Crucially, with studies identifying the molecular mechanisms by which DAMPs promote immune suppression, therapeutic strategies that prevent and/or reverse DAMP-induced immunosuppression have been proposed. Approaches currently under consideration include the use of synthetic polymers, or the delivery of plasma proteins, to scavenge circulating DAMPs, or to treat critically-injured patients with antagonists of DAMP receptors. However, as DAMPs share signalling pathways with pathogen associated molecular patterns, and pro-inflammatory responses are essential for tissue regeneration, these approaches need to be carefully considered in order to ensure that modulating DAMP levels and/or their interaction with immune cells does not negatively impact upon anti-microbial defence and the physiological responses of tissue repair and wound healing.
Topics: Humans; Immunosuppression Therapy; Infertility; Immunomodulation; Alarmins; Cross Infection
PubMed: 37662933
DOI: 10.3389/fimmu.2023.1239683 -
Research progress on the immunomodulatory mechanism of acupuncture in tumor immune microenvironment.Frontiers in Immunology 2023With the constantly deeper understanding of individualized precision therapy, immunotherapy is increasingly developed and personalized. The tumor immune microenvironment... (Review)
Review
With the constantly deeper understanding of individualized precision therapy, immunotherapy is increasingly developed and personalized. The tumor immune microenvironment (TIME) mainly consists of infiltrating immune cells, neuroendocrine cells, extracellular matrix, lymphatic vessel network, etc. It is the internal environment basis for the survival and development of tumor cells. As a characteristic treatment of traditional Chinese medicine, acupuncture has shown potentially beneficial impacts on TIME. The currently available information demonstrated that acupuncture could regulate the state of immunosuppression through a range of pathways. An effective way to understand the mechanisms of action of acupuncture was to analyze the response following treatment of the immune system. This research reviewed the mechanisms of acupuncture regulating tumor immunological status based on innate and adaptive immunity.
Topics: Acupuncture Therapy; Immunomodulation; Immunotherapy; Immunosuppression Therapy; Adaptive Immunity
PubMed: 36865562
DOI: 10.3389/fimmu.2023.1092402 -
International Journal of Surgery... Nov 2015Cell therapy for Type 1 diabetes (T1D) utilizing islet cell transplantation can successfully restore endogenous insulin production in affected patients. Islet cell... (Review)
Review
Cell therapy for Type 1 diabetes (T1D) utilizing islet cell transplantation can successfully restore endogenous insulin production in affected patients. Islet cell engraftment and survival are conditional on the use of efficacious anti-rejection therapies and on the availability of healthy donor cells. The scarcity of healthy human donor pancreata is a limiting factor in providing sufficient tissue to meet the demand for islet transplantation worldwide. A potential alternative to the use of cadaveric human donor pancreases is the use of animal sourced islets. Pancreatic islets obtained from pigs have emerged as an alternative to human tissues due to their great availability, physiological similarities to human islets, including the time-tested use of porcine insulin in diabetic patients and the ability to genetically modify the donor source. The evolution of refined, efficacious immunosuppressive therapies with reduced toxicity, improvements in donor management and genetic manipulation of the donor have all contributed to facilitate long-term function in pre-clinical models of pig islet grafts in non-human primates. As clinical consideration for this option is growing, and trials involving the use of porcine islets have begun, more compelling experimental data suggest that the use of pig islets may soon become a viable, safe, effective and readily available treatment for insulin deficiency in T1D patients.
Topics: Animals; Diabetes Mellitus, Type 1; Graft Rejection; Humans; Immunosuppression Therapy; Islets of Langerhans Transplantation; Primates; Swine; Tissue Donors; Transplantation, Heterologous
PubMed: 26253846
DOI: 10.1016/j.ijsu.2015.07.703 -
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 -
American Journal of Transplantation :... Aug 2017It is estimated that solid organ transplant recipients have a two- to fourfold greater overall risk of malignancy than the general population. Some of the most common... (Review)
Review
It is estimated that solid organ transplant recipients have a two- to fourfold greater overall risk of malignancy than the general population. Some of the most common malignancies after transplant include skin cancers and posttransplant lymphoproliferative disorder. In addition to known risk factors such as environmental exposures, genetics, and infection with oncogenic viruses, immunosuppression plays a large role in the development of cancer through the loss of the immunosurveillance process. The purpose of this article is to explain the role of immunosuppression in cancer and to review the classes of chemotherapeutics. The field of anticancer drugs is continually expanding and developing, with limited data on use in transplant recipients. This article aims to provide information on class review, adverse effects, dose adjustments, and drug interactions that are pertinent to the care of transplant recipients.
Topics: Antineoplastic Agents; Humans; Immune Tolerance; Immunosuppression Therapy; Neoplasms; Organ Transplantation; Transplant Recipients
PubMed: 28394486
DOI: 10.1111/ajt.14238 -
Seminars in Oncology Aug 2015The PD-1 pathway, comprising the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates local immunosuppression in... (Review)
Review
The PD-1 pathway, comprising the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates local immunosuppression in the tumor microenvironment. Drugs designed to block PD-1 or PD-L1 "release the brakes" on anti-tumor immunity and have demonstrated clinical activity in several types of advanced cancers, validating this pathway as a target for cancer therapy. Two such drugs have recently been approved to treat melanoma and lung cancers, and regulatory approvals in first- and second-line settings for additional cancer types are anticipated. The manageable safety profile of PD-1/PD-L1 blocking drugs identifies them as suitable for outpatient administration and the development of combinatorial therapies. Ongoing studies aim to identify biomarkers to guide patient selection, which would further improve the risk:benefit ratio for these drugs.
Topics: Antineoplastic Agents; B7-H1 Antigen; Biomarkers, Tumor; Humans; Immunosuppression Therapy; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment
PubMed: 26320063
DOI: 10.1053/j.seminoncol.2015.05.013 -
Clinics in Laboratory Medicine Mar 2019Immunosuppression is essential to prevent graft rejection. However, immunosuppression impairs the ability of the host immune system to control viral infection and... (Review)
Review
Immunosuppression is essential to prevent graft rejection. However, immunosuppression impairs the ability of the host immune system to control viral infection and decreases tumor immunosurveillance. Therefore, immunosuppression after organ transplantation is a major risk factor for posttransplantation cancer. Notably, recent reports suggest that immunosuppressive agents can activate tumorigenic pathways independent of the involvement of the host immune system. In this review, we focus on cell-intrinsic tumorigenic pathways directly activated by immunosuppressive agents and discuss the much-described infection- and immune-mediated mechanisms of cancer development in organ transplant recipients.
Topics: Cytokines; Humans; Immunosuppression Therapy; Neoplasms; Organ Transplantation; Receptors, Chemokine; Signal Transduction
PubMed: 30709505
DOI: 10.1016/j.cll.2018.10.006