Immune checkpoint inhibitors have progressed rapidly over the past decade and have become one of the most promising oncology treatments. However, immune checkpoint inhibitors reduce T-cell tolerance and lead to a unique spectrum of immune-related adverse events (IRAE). IRAE can involve multiple systems, including endocrine, gastrointestinal, respiratory and skin systems and there is no predictive marker with high specificity and sensitivity. Mild IRAE can be alleviated by discontinuing immune checkpoint inhibitors while severe IRAEs require active intervention. The first-line treatment is glucocorticoids, and immunosuppressants can be considered in refractory cases. However the optimal choice of immunosuppressants is currently controversial. This review provides an overview of the epidemiology and possible mechanisms of immune-related adverse events, outlines some promising predictive biomarkers, and describes several immunotherapy-related organ toxicity and management.
Humans ; Immunologic Factors/adverse effects* ; Immunosuppressive Agents ; Immunotherapy/adverse effects*

Humans ; Immunosuppressive Agents ; adverse effects ; Lymphoma ; chemically induced ; Methotrexate ; adverse effects

OBJECTIVETacrolimus (FK506) is an immunosuppressive drug, which is widely used to prevent rejection of transplanted organs. However, chronic administration of FK506 leads to hypertension in solid organ transplantation patients, and its molecular mechanisms are much more complicated. In this review, we will discuss the above-mentioned molecular mechanisms of FK506-induced hypertension in solid organ transplantation subjects.

DATA SOURCESThe data analyzed in this review were mainly from relevant articles without restriction on the publication date reported in PubMed. The terms "FK506" or "tacrolimus" and "hypertension" were used for the literature search.

STUDY SELECTIONOriginal articles with no limitation of research design and critical reviews containing data relevant to FK506-induced hypertension and its molecular mechanisms were retrieved, reviewed and analyzed.

RESULTSThere are several molecular mechanisms attributed to FK506-induced hypertension in solid organ transplantation subjects. First, FK506 binds FK506 binding protein 12 and its related isoform 12.6 (FKBP12/12.6) and removes them from intracellular ryanodine receptors that induce a calcium ion leakage from the endoplasmic/sarcoplasmic reticulum. The conventional protein kinase C beta II (cPKCβII)-mediated phosphorylation of endothelial nitric oxide (NO) synthase at Thr495, which reduces the production of NO, was activated by calcium ion leakage. Second, transforming growth factor receptor/SMAD2/3 signaling activation plays an important role in Treg/Th17 cell imbalance in T cells which toget converge to cause inflammation, endothelial dysfunction, and hypertension following tacrolimus treatment. Third, the activation of with-no-K(Lys) kinases/STE20/SPS1-related proline/alanine-rich kinase/thiazide-sensitive sodium chloride co-transporter (WNKs/SPAK/NCC) pathway has a central role in tacrolimus-induced hypertension. Finally, the enhanced activity of renal renin-angiotensin-aldosterone system seems to play a crucial role in the pathophysiology of FK506-induced hypertension.

CONCLUSIONFK506 plays a predominant role in the pathophysiology of hypertension in solid organ transplantation subjects.

Humans ; Hypertension ; chemically induced ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Organ Transplantation ; adverse effects ; Tacrolimus ; adverse effects ; therapeutic use

Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Humans ; Immunosuppressive Agents ; pharmacology ; Tripterygium ; adverse effects ; chemistry

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.
Humans ; Child ; Prednisone/adverse effects* ; Tacrolimus/adverse effects* ; Retrospective Studies ; Activities of Daily Living ; Immunosuppressive Agents/adverse effects* ; Myasthenia Gravis/drug therapy* ; Glucocorticoids/therapeutic use* ; Mycophenolic Acid/adverse effects*

Adjuvants, Immunologic ; administration & dosage ; adverse effects ; Child ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; Pediatrics ; Practice Guidelines as Topic ; Treatment Outcome

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.
Humans ; Mycophenolic Acid/adverse effects* ; Azathioprine/adverse effects* ; Tacrolimus/therapeutic use* ; Lupus Nephritis/complications* ; Immunosuppressive Agents ; Treatment Outcome ; Recurrence

The number of children undergoing successful renal transplantations has been increasing steadily and as a result, general pediatricians are now more likely to encounter children with a kidney allograft in their practice. Although the medical care immediately after transplantation is mostly provided by transplant teams, more and more outpatient care will eventually be performed at the patient's local community. Medical care from general pediatricians is particularly important, especially for children who are residing far from transplant centers. As these children require prolong immunosuppressive therapies and are susceptible to various specific clinical problems, it is imperative for their primary care providers and pediatricians to be knowledgeable about their specific needs and be competent in providing care. This article highlights the roles and common practice related issues that pertain to general pediatricians in the care of pediatric renal allograft recipients.
Child ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; psychology ; Pediatrics ; Vaccination

Treatment of myelodysplastic syndrome (MDS) remains unsatisfactory. It is possible that immunosuppressive therapy might be effective for a certain subset of patients with MDS. In this review 105 patients with MDS who were treated with cyclosporin A (CsA) including 90 RA, 5 RARS, 10 RAEB, were analyzed. The dose of CsA was 2 - 12 mg/(kg x d) for at least three months. Hematological improvement was observed in 64 patients (61%), and complete remission was observed in 14 patients (13.3%). These results indicated that CsA immunosuppressive therapy may be useful for IPSS low, intermediate-1 and intermediate-2 MDS patients.
Cyclosporine ; adverse effects ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Myelodysplastic Syndromes ; drug therapy ; immunology

Calcineurin inhibitors (CNIs) are playing an important role in preventing acute rejection in renal transplantation; however, their nephrotoxicity may impact long-term renal allograft survival. Several CNI-sparing regimens (such as CNI-avoidance or CNI-minimization) have shown at least comparable efficacy with standard-dose CNI regimens. Research continues to achieve the "best" balance between efficacy and toxicity of available immunosuppressive regimens.
Calcineurin Inhibitors ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; Kidney Transplantation