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Seminars in Nephrology Jan 2024Post-transplant lymphoproliferative disorders (PTLDs) are a heterogenous set of unregulated lymphoid cell proliferations after organ or tissue transplant. A majority of... (Review)
Review
Post-transplant lymphoproliferative disorders (PTLDs) are a heterogenous set of unregulated lymphoid cell proliferations after organ or tissue transplant. A majority of cases are associated with the Epstein-Barr virus and higher intensity of pharmacologic immunosuppression. The clinical presentations are numerous. The diagnosis is ideally by histology, except in cases where the tumor is inaccessible to biopsy. While some pre-emptive therapies and treatment strategies are available have reasonable success are available, they do not eliminate the high morbidity and significant mortality after PTLD.
Topics: Humans; Lymphoproliferative Disorders; Epstein-Barr Virus Infections; Immunosuppressive Agents; Postoperative Complications; Kidney Transplantation; Herpesvirus 4, Human; Organ Transplantation; Immunosuppression Therapy
PubMed: 38519279
DOI: 10.1016/j.semnephrol.2024.151503 -
Journal of Pharmacy & Pharmaceutical... 2023Aplastic anemia (AA) is a bone marrow failure disease caused by T cell hyperfunction. Although the overall response rate has been improved by immunosuppressive therapy... (Review)
Review
Aplastic anemia (AA) is a bone marrow failure disease caused by T cell hyperfunction. Although the overall response rate has been improved by immunosuppressive therapy (IST) plus Eltrombopag, 30% of patients have either no response or relapse. We therefore attempted to find other ways to improve the outcomes of AA patients. Traditional Chinese medicine has the advantages of low cost, reasonable effects, and few side effects. More and more clinical studies have confirmed that traditional Chinese medicine has a beneficial role in treating AA patients. This article reviews the potential mechanism of traditional Chinese medicine or its active ingredients in the treatment of AA. These include improving the bone marrow microenvironment, regulating immunity, and affecting the fate of hematopoietic stem cells. This provides useful information for further treatment of AA with integration of traditional Chinese and Western medicine and the development of new treatment strategies.
Topics: Humans; Anemia, Aplastic; Medicine, Chinese Traditional; Immunosuppression Therapy; Recurrence; Immunosuppressive Agents
PubMed: 38022904
DOI: 10.3389/jpps.2023.11863 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Kidney transplant (KT) recipients of HLA identical siblings (HLAid) have lower immunological risk, but there are no specific recommendations for immunosuppression. Our... (Review)
Review
BACKGROUND
Kidney transplant (KT) recipients of HLA identical siblings (HLAid) have lower immunological risk, but there are no specific recommendations for immunosuppression. Our aim was to analyze evidence about results from HLAid living-donor recipients under different immunosuppression in the current era of immunological risk assessment.
METHODS
Systematic review of studies describing associations between outcomes of HLAid living-donor KT recipients according to their immunological risk and applied immunosuppression.
RESULTS
From 1351 studies, 16 (5636 KT recipients) were included in the analysis. All studies were retrospective, ten comparing immunosuppression strategies, and six immunological risk strata. Of those ten, six studies were published in 1990 or earlier and only three included tacrolimus. The evidence is poor, and the inclusion of calcineurin inhibitors does not demonstrate better results. Furthermore, only few studies describe different immunosuppression regimens according to the patient immunological risk and, in general, they do not include the assessment with new solid phase assays.
CONCLUSIONS
There are no studies analyzing the association of outcomes of HLAid KT recipients with current immunological risk tools. In the absence of evidence, no decision or proposal of immunosuppression adapted to modern immunological risk assessment can be made currently by the Descartes Working Group.
Topics: Humans; Kidney Transplantation; Living Donors; Retrospective Studies; Graft Survival; Graft Rejection; Immunosuppression Therapy; Transplant Recipients; Immunosuppressive Agents; HLA Antigens
PubMed: 37657355
DOI: 10.1016/j.trre.2023.100787 -
The Veterinary Quarterly Dec 2023Certain pathogens, due to their adverse effects on the immune reaction, aggravate the course of concomitant heterologous infections. Here we summarize mechanisms by... (Review)
Review
Certain pathogens, due to their adverse effects on the immune reaction, aggravate the course of concomitant heterologous infections. Here we summarize mechanisms by which circoviruses, including the most studied porcine circovirus 2, and other mammalian and avian circoviruses, trigger their own replication and confound the hosts' immune response. At different stages of infection, from latent state to disease induction, these viruses markedly influence the cellular signaling pathways. Circoviruses have been found to interfere with interferon and proinflammatory cytokine producing and responsive pathways. Apoptotic processes, altered cellular transport and constraint of the mitotic phase all support the viral replication. The cytokine imbalance and lymphocyte depletion, thus the impaired immunity, favors invasion of super- or co-infecting agents, which in concert with circoviruses induce illnesses with increased severity. The information summarized in this review point out the diversity of host and viral factors involved in the mechanisms of disease progression during circovirus infections.
Topics: Swine; Animals; Circovirus; Circoviridae Infections; Virus Replication; Immunosuppression Therapy; Cytokines; Swine Diseases; Mammals
PubMed: 37431709
DOI: 10.1080/01652176.2023.2234430 -
Frontiers in Immunology 2024Regulatory cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a crucial role in preserving immune... (Review)
Review
Regulatory cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a crucial role in preserving immune tolerance and controlling immune responses during infections to prevent excessive immune activation. However, pathogens have developed strategies to hijack these regulatory cells to decrease the overall effectiveness of the immune response and persist within the host. Consequently, therapeutic targeting of these immunosuppressive mechanisms during infection can reinvigorate the immune response and improve the infection outcome. The suppressive mechanisms of regulatory cells are not only numerous but also redundant, reflecting the complexity of the regulatory network in modulating the immune responses. The context of the immune response, such as the type of pathogen or tissue involved, further influences the regulatory mechanisms involved. Examples of these immunosuppressive mechanisms include the production of inhibitory cytokines such as interleukin 10 (IL-10) and transforming growth factor beta (TGF-β) that inhibit the production of pro-inflammatory cytokines and dampen the activation and proliferation of effector T cells. In addition, regulatory cells utilize inhibitory receptors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to engage with their respective effector cells, thereby suppressing their function. An alternative approach involves the modulation of metabolic reprogramming in effector immune cells to limit their activation and proliferation. In this review, we provide an overview of the major mechanisms mediating the immunosuppressive effect of the different regulatory cell subsets in the context of infection.
Topics: T-Lymphocytes, Regulatory; Immune Tolerance; Cytokines; Transforming Growth Factor beta; Immunosuppression Therapy
PubMed: 38380317
DOI: 10.3389/fimmu.2024.1328193 -
Molecular Cancer Apr 2024Cancer progression is continuously controlled by the immune system which can identify and destroy nascent tumor cells or inhibit metastatic spreading. However, the... (Review)
Review
Cancer progression is continuously controlled by the immune system which can identify and destroy nascent tumor cells or inhibit metastatic spreading. However, the immune system and its deregulated activity in the tumor microenvironment can also promote tumor progression favoring the outgrowth of cancers capable of escaping immune control, in a process termed cancer immunoediting. This process, which has been classified into three phases, i.e. "elimination", "equilibrium" and "escape", is influenced by several cancer- and microenvironment-dependent factors. Senescence is a cellular program primed by cells in response to different pathophysiological stimuli, which is based on long-lasting cell cycle arrest and the secretion of numerous bioactive and inflammatory molecules. Because of this, cellular senescence is a potent immunomodulatory factor promptly recruiting immune cells and actively promoting tissue remodeling. In the context of cancer, these functions can lead to both cancer immunosurveillance and immunosuppression. In this review, the authors will discuss the role of senescence in cancer immunoediting, highlighting its context- and timing-dependent effects on the different three phases, describing how senescent cells promote immune cell recruitment for cancer cell elimination or sustain tumor microenvironment inflammation for immune escape. A potential contribution of senescent cells in cancer dormancy, as a mechanism of therapy resistance and cancer relapse, will be discussed with the final objective to unravel the immunotherapeutic implications of senescence modulation in cancer.
Topics: Humans; Neoplasms; Cellular Senescence; Immune System; Immunosuppression Therapy; Tumor Microenvironment
PubMed: 38561826
DOI: 10.1186/s12943-024-01973-5 -
Critical Care Clinics Jan 2024Heart transplantation (HT) remains the best treatment of patients with severe heart failure who are deemed to be transplant candidates. The authors discuss postoperative... (Review)
Review
Heart transplantation (HT) remains the best treatment of patients with severe heart failure who are deemed to be transplant candidates. The authors discuss postoperative management of the HT recipient by system, emphasizing areas where care might differ from other cardiac surgery patients. Working together, critical care physicians, heart transplant surgeons and cardiologists, advanced practice providers, pharmacists, transplant coordinators, nursing staff, physical therapists, occupational therapists, rehabilitation specialists, nutritionists, health psychologists, social workers, and the patient and their loved ones partner to increase the likelihood of a successful outcome.
Topics: Humans; Graft Rejection; Heart Transplantation; Immunosuppression Therapy; Critical Care; Heart Failure
PubMed: 37973350
DOI: 10.1016/j.ccc.2023.05.004 -
Life Sciences Apr 2024The immune cells within the tumor microenvironment (TME) exert multifaceted functions ranging from tumor-antagonizing or tumor-promoting activities. During the initial... (Review)
Review
The immune cells within the tumor microenvironment (TME) exert multifaceted functions ranging from tumor-antagonizing or tumor-promoting activities. During the initial phases of tumor development, the tumor-antagonizing immune cells in the TME combat cancer cells in an immune surveillance process. However, with time, cancer cells can evade detection and impede the immune cells' effectiveness through diverse mechanisms, such as decreasing immunogenic antigen presentation on their surfaces and/or secreting anti-immune factors that cause tolerance in TME. Moreover, some immune cells cause immunosuppressive situations and inhibit antitumoral immune responses. Physical and cellular-mediated barriers in the TME, such as cancer-associated fibroblasts, tumor endothelium, the altered lipid composition of tumor cells, and exosomes secreted from cancer cells, also mediate immunosuppression and prevent extravasation of immune cells. Due to successful clinical outcomes of cancer treatment strategies the potential barriers must be identified and addressed. We need to figure out how to optimize cancer immunotherapy strategies, and how to combine therapeutic approaches for maximum clinical benefit. This review provides a detailed overview of various cells and molecules in the TME, their association with escaping from immune surveillance, therapeutic targets, and future perspectives for improving cancer immunotherapy.
Topics: Humans; Monitoring, Immunologic; Neoplasms; Immunotherapy; Immunosuppression Therapy; Immunity; Tumor Microenvironment
PubMed: 38408406
DOI: 10.1016/j.lfs.2024.122528 -
Advanced Drug Delivery Reviews Sep 2023The rising incidence and persistent thrombosis in multiple cancers including those that are immunosuppressive highlight the need for understanding the tumor coagulome... (Review)
Review
The rising incidence and persistent thrombosis in multiple cancers including those that are immunosuppressive highlight the need for understanding the tumor coagulome system and its role beyond hemostatic complications. Immunotherapy has shown significant benefits in solid organ tumors but has been disappointing in the treatment of hypercoagulable cancers, such as glioblastoma and pancreatic ductal adenocarcinomas. Thus, targeting thrombosis to prevent immunosuppression seems a clinically viable approach in cancer treatment. Hypercoagulable tumors often develop fibrin clots within the tumor microenvironment (TME) that dictates the biophysical characteristics of the tumor tissue. The application of systems biology and single-cell approaches highlight the potential role of coagulome or thrombocytosis in shaping the tumor immune microenvironment (TIME). In-depth knowledge of the tumor coagulome would provide unprecedented opportunities to better predict the hemostatic complications, explore how thrombotic stroma modulates tumor immunity, reexamine the significance of clinical biomarkers, and enable steering the stromal versus systemic immune response for boosting the effectiveness of immune checkpoint inhibitors in cancer treatment. We focus on the role of coagulation factors in priming a suppressive TIME and the huge potential of existing anticoagulant drugs in the clinical settings of cancer immunotherapy.
Topics: Humans; Tumor Microenvironment; Immunotherapy; Pancreatic Neoplasms; Immunosuppression Therapy; Carcinoma, Pancreatic Ductal
PubMed: 37517779
DOI: 10.1016/j.addr.2023.115027 -
Frontiers in Immunology 2024The effectiveness of tumor therapy, especially immunotherapy and oncolytic virotherapy, critically depends on the activity of the host immune cells. However, various... (Review)
Review
The effectiveness of tumor therapy, especially immunotherapy and oncolytic virotherapy, critically depends on the activity of the host immune cells. However, various local and systemic mechanisms of immunosuppression operate in cancer patients. Tumor-associated immunosuppression involves deregulation of many components of immunity, including a decrease in the number of T lymphocytes (lymphopenia), an increase in the levels or ratios of circulating and tumor-infiltrating immunosuppressive subsets [e.g., macrophages, microglia, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs)], as well as defective functions of subsets of antigen-presenting, helper and effector immune cell due to altered expression of various soluble and membrane proteins (receptors, costimulatory molecules, and cytokines). In this review, we specifically focus on data from patients with glioblastoma/glioma before standard chemoradiotherapy. We discuss glioblastoma-related immunosuppression at baseline and the prognostic significance of different subsets of circulating and tumor-infiltrating immune cells (lymphocytes, CD4+ and CD8+ T cells, Tregs, natural killer (NK) cells, neutrophils, macrophages, MDSCs, and dendritic cells), including neutrophil-to-lymphocyte ratio (NLR), focus on the immune landscape and prognostic significance of isocitrate dehydrogenase ()-mutant gliomas, proneural, classical and mesenchymal molecular subtypes, and highlight the features of immune surveillance in the brain. All attempts to identify a reliable prognostic immune marker in glioblastoma tissue have led to contradictory results, which can be explained, among other things, by the unprecedented level of spatial heterogeneity of the immune infiltrate and the significant phenotypic diversity and (dys)functional states of immune subpopulations. High NLR is one of the most repeatedly confirmed independent prognostic factors for shorter overall survival in patients with glioblastoma and carcinoma, and its combination with other markers of the immune response or systemic inflammation significantly improves the accuracy of prediction; however, more prospective studies are needed to confirm the prognostic/predictive power of NLR. We call for the inclusion of dynamic assessment of NLR and other blood inflammatory markers (e.g., absolute/total lymphocyte count, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, and systemic immune response index) in all neuro-oncology studies for rigorous evaluation and comparison of their individual and combinatorial prognostic/predictive significance and relative superiority.
Topics: Humans; Glioblastoma; Prognosis; Immunosuppression Therapy; Glioma; Killer Cells, Natural; Inflammation
PubMed: 38481999
DOI: 10.3389/fimmu.2024.1326753