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International Journal of Molecular... May 2024Inflammatory skin diseases highlight inflammation as a central driver of skin pathologies, involving a multiplicity of mediators and cell types, including immune and... (Review)
Review
Inflammatory skin diseases highlight inflammation as a central driver of skin pathologies, involving a multiplicity of mediators and cell types, including immune and non-immune cells. Adenosine, a ubiquitous endogenous immune modulator, generated from adenosine triphosphate (ATP), acts via four G protein-coupled receptors (A, A, A, and A). Given the widespread expression of those receptors and their regulatory effects on multiple immune signaling pathways, targeting adenosine receptors emerges as a compelling strategy for anti-inflammatory intervention. Animal models of psoriasis, contact hypersensitivity (CHS), and other dermatitis have elucidated the involvement of adenosine receptors in the pathogenesis of these conditions. Targeting adenosine receptors is effective in attenuating inflammation and remodeling the epidermal structure, potentially showing synergistic effects with fewer adverse effects when combined with conventional therapies. What is noteworthy are the promising outcomes observed with A agonists in animal models and ongoing clinical trials investigating A agonists, underscoring a potential therapeutic approach for the management of inflammatory skin disorders.
Topics: Humans; Animals; Adenosine; Receptors, Purinergic P1; Skin Diseases; Dermatitis; Inflammation; Psoriasis; Signal Transduction; Anti-Inflammatory Agents
PubMed: 38891997
DOI: 10.3390/ijms25115810 -
Cells Jun 2024Chimerism analysis after allogeneic hematopoietic stem cell transplantation serves to confirm engraftment, indicate relapse of hematologic malignancy, and attribute... (Review)
Review
Chimerism analysis after allogeneic hematopoietic stem cell transplantation serves to confirm engraftment, indicate relapse of hematologic malignancy, and attribute graft failure to either immune rejection or poor graft function. Short tandem repeat PCR (STR-PCR) is the prevailing method, followed by quantitative real-time PCR (qPCR), with detection limits of 1-5% and 0.1%, respectively. Chimerism assays using digital PCR or next-generation sequencing, both of which are more sensitive than STR-PCR, are increasingly used. Stable mixed chimerism is usually not associated with poor outcomes in non-malignant diseases, but recipient chimerism may foretell relapse of hematologic malignancies, so higher detection sensitivity may be beneficial in such cases. Thus, the need for and the type of intervention, e.g., immunosuppression regimen, donor lymphocyte infusion, and/or salvage second transplantation, should be guided by donor chimerism in the context of the feature and/or residual malignant cells of the disease to be treated.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Chimerism; Transplantation Chimera; Hematologic Neoplasms
PubMed: 38891125
DOI: 10.3390/cells13110993 -
Journal of Nanobiotechnology Jun 2024Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely...
BACKGROUND
Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated.
RESULTS
This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors.
CONCLUSIONS
These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Animals; Hydrogels; Nanocomposites; Humans; Mice; Radiofrequency Ablation; Sumoylation; Cell Line, Tumor; Male
PubMed: 38890737
DOI: 10.1186/s12951-024-02579-1 -
Journal of Investigational Allergology... Jun 2024
Successful Desensitization to Isatuximab in a Patient With Refractory Multiple Myeloma and Indolent Systemic Mastocytosis. Reply to: Anaphylactic Shock due to Isatuximab and Successful Desensitization.
Topics: Humans; Multiple Myeloma; Anaphylaxis; Mastocytosis, Systemic; Desensitization, Immunologic; Antibodies, Monoclonal, Humanized; Drug Hypersensitivity
PubMed: 38888584
DOI: 10.18176/jiaci.0990 -
Journal For Immunotherapy of Cancer Jun 2024The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally...
The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.
Topics: Humans; Disease Progression; Oncolytic Virotherapy; Oncolytic Viruses; Neoplasms; Adenoviridae
PubMed: 38886116
DOI: 10.1136/jitc-2024-008809 -
CMAJ : Canadian Medical Association... Jun 2024
Review
Topics: Humans; Food Hypersensitivity; Infant; Child, Preschool; Administration, Oral; Desensitization, Immunologic; Allergens
PubMed: 38885980
DOI: 10.1503/cmaj.231478 -
Cureus May 2024A 75-year-old woman, with hypertension and atrial fibrillation but no prior renal history, presented to the hospital for chest discomfort and dyspnea. She was found to...
A 75-year-old woman, with hypertension and atrial fibrillation but no prior renal history, presented to the hospital for chest discomfort and dyspnea. She was found to be in acute renal failure, with a serum creatinine of 5.1, increased from a baseline of 0.9, and urine analysis revealing proteinuria and hematuria with dysmorphic red blood cells. Subsequent work up was significant for positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and myeloperoxidase antibodies. She underwent a renal biopsy, which revealed necrotizing crescents in 12 of 14 glomeruli, and she was diagnosed with rapidly progressive glomerulonephritis due to microscopic polyangiitis. Despite aggressive treatment with plasmapheresis, high-dose prednisone, and rituximab infusions, renal function worsened, and she required initiation of hemodialysis. She was ultimately discharged after a three-week admission, with plans to continue rituximab infusions and three times weekly hemodialysis in the outpatient setting. Due to her poor response to traditional therapies, initiation of a new targeted immunomodulator known as avacopan, a complement 5a receptor antagonist, was considered. Such targeted immunomodulators are also of particular interest as possible ways to reduce the risk of severe infection associated with current broad immunosuppressive modalities. In addition, when used in place of steroids, they reduce the morbidity associated with cumulative glucocorticoid toxicity. For patients with ANCA-associated vasculitis refractory to standard therapies, targeted immunomodulators such as avacopan should be considered as alternative or adjunct therapy.
PubMed: 38883118
DOI: 10.7759/cureus.60366 -
Cureus May 2024Secondary organizing pneumonia (SOP) as a sequela to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually has a prolonged benign course with a good...
Secondary organizing pneumonia (SOP) as a sequela to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually has a prolonged benign course with a good response to corticosteroids. We present a case series of three patients who developed rapid progression to organizing pneumonia, after initial presentation with SARS-CoV-2. Imaging revealed rapid interval progression of bilateral subpleural ground glass opacities, and lung biopsy showed dense fibroblastic plugs within the alveoli. Two patients were steroid-responsive, and one patient succumbed to his illness despite maximal therapy. We postulate that B-cell depletion and immunosuppression may cause rapid progression to SOP, as all three patients were immunosuppressed and on chronic rituximab therapy.
PubMed: 38883063
DOI: 10.7759/cureus.60328 -
Cureus May 2024Histoplasmosis is a fungal infection caused by the fungus . It can manifest in various ways, ranging from pulmonary to disseminated presentations. Most of the...
Histoplasmosis is a fungal infection caused by the fungus . It can manifest in various ways, ranging from pulmonary to disseminated presentations. Most of the disseminated cases are seen in immunocompromised patients; here, we present an unusual case of an 81-year-old Mexican male with a history of cave exposure in his childhood, with 75 years of incubation period of the disease, who developed disseminated cutaneous histoplasmosis with no evident immunocompromising conditions. We considered the hypotheses of transient immunosuppression, CD4+ T lymphocytopenia, and immune senescence as the cause of this manifestation. The present case is also notable for its recurrence following therapy. This report underscores the challenges in diagnosing histoplasmosis in immunocompetent individuals and highlights the importance of long-term treatment and follow-up.
PubMed: 38883060
DOI: 10.7759/cureus.60433 -
Cureus May 2024Hemolytic uremic syndrome (HUS) is a prevalent cause of severe acute kidney injury in children, often leading to chronic renal damage. It is characterized by thrombotic...
Hemolytic uremic syndrome (HUS) is a prevalent cause of severe acute kidney injury in children, often leading to chronic renal damage. It is characterized by thrombotic microangiopathy (TMA), which represents a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The choice of treatment and management strategies depends primarily on the underlying etiology. We present the case of a two-year-old girl diagnosed with rapidly progressive glomerulonephritis accompanied by hypertension necessitating renal replacement therapy. Initial laboratory findings indicated positive antinuclear antibodies, prompting immunosuppression and renal biopsy, revealing TMA with minimal chronicity changes. The treatment involved plasmapheresis and a single dose of injection rituximab, resulting in clinical recovery with an improved glomerular filtration rate. Since the anti-complement factor H antibody result was negative, the genetic etiology of atypical HUS was considered. The patient was discharged with favorable outcomes, including normal urine output and the absence of edema. This case concludes that young children with atypical HUS may present with a severe clinical course necessitating early intervention. The lack of genetic analysis facilities in severe cases should not hinder the timely initiation of plasmapheresis to prevent further injury and progression to chronic kidney disease.
PubMed: 38883005
DOI: 10.7759/cureus.60502