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Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies.

Advanced therapy medicinal products (ATMPs) are medicines for human use based on genes, cells or tissue engineering. After clear successes in adults, the nascent technology now sees increasing pediatric application. For many still untreatable disorders with pre- or perinatal onset, timely intervention is simply indispensable; thus, prenatal and pediatric applications of ATMPs hold great promise for curative treatments. Moreover, for most inherited disorders, early ATMP application may substantially improve efficiency, economy and accessibility compared with application in adults. Vindicating t

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, the high resistance has become the most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), the light chain of major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one of the key mechanisms underlying tumor immunotherapy resistance. Therefore, eluci

Characteristics and outcomes of Bahraini pediatric patients sent abroad for bone marrow transplantation: A ten-year retrospective cohort study.

BackgroundBone marrow transplantation (BMT) is a breakthrough procedure for patients with hematological and oncological conditions, particularly when all other treatments fail. Its indications vary between patients and settings, and its outcomes depend on the donor type, transplantation facility, and center expertise. In countries where transplantation facilities are lacking, sending patients abroad for transplantation might be a safe and effective alternative to leaving the patient to face eventual disease morbidity or even mortality if the procedure is not performed locally. However, studies

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveill

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… Human eosinophils have been reported to induce colon cancer cell death in vitro , implying mechanisms involving innate receptors (TCRγδ/CD3 complex, TLR2) and mediators such as alpha‐defensins, TNF‐α, granzyme A and IL‐18 56 , 57 , 58 . … A functional gammadeltaTCR/CD3 complex distinct from gammadeltaT cells is expressed by human eosinophils. PLoS One 2009;4:e5926. 59. Karagiannis SN, Bracher MG, Hunt J, McCloskey N, Beavil RL, Beavil AJ et al. …

The role of CD8+ T cells in the immunoregulation of osteoporosis.

INTRODUCTION: Osteoporosis weakens the skeleton by lowering bone mass and damaging bone microarchitecture. A growing body of evidence points to disruptions in osteoimmune homeostasis as a key driver of this disease. In particular, apoptosis of bone cells and immune cells appears to be a critical contributing mechanism. Within the bone marrow, CD8+ T cells display a surprising functional duality: whether they protect bone or promote its loss depends heavily on local signals. Under healthy conditions or after mechanical loading, activated CD8+ T cells help maintain bone mass. They do so mainly b

Artificial Intelligence in Bone Marrow Histological Diagnostics: Potential Applications and Challenges.

The expanding digitalization of routine diagnostic histological slides holds a potential to apply artificial intelligence (AI) to pathology, including bone marrow (BM) histology. In this perspective, we describe potential tasks in diagnostics that can be supported, investigations that can be guided, and questions that can be answered by the future application of AI on whole-slide images of BM biopsies. These range from characterization of cell lineages and quantification of cells and stromal structures to disease prediction. First glimpses show an exciting potential to detect subtle phenotypic

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

Clinical transplantation and tolerance: are we there yet?

Organ transplantation is not only considered as the last resort therapy but also as the treatment of choice for many patients with end-stage organ damage. Recipient-mediated acute or chronic immune response is the main challenge after transplant surgery. Nonspecific suppression of host immune system is currently the only method used to prevent organ rejection. Lifelong immunosuppression will cause significant side effects such as infections, malignancies, chronic kidney disease, hypertension and diabetes. This is more relevant in children who have a longer life expectancy so may receive longer

Pyoderma gangrenosum: pathogenetic mechanisms and their implications for treatment.

Pyoderma gangrenosum (PG) is a rare inflammatory skin disease belonging to the group of neutrophilic dermatoses. The pathogenesis of PG involves a predisposing genetic background that facilitates a dysregulated innate and adaptive immune response, with an imbalance between pro-inflammatory and anti-inflammatory mediators, leading to neutrophil-driven inflammatory damage. Several immunosuppressants and immunomodulatory drugs are currently available for the treatment of PG, in combination with topical therapies, wound management and pain control strategies. Systemic corticosteroids and cyclospor

IgG replacement in multiple myeloma.

T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation t

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Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on patients' symptoms.ObjectiveTo evaluate feasibility and toxicity of plasma-cell targeting treatment using the subcutan

The role of CD38 in HIV infection.

The widely-expressed molecule CD38 is a single-stranded type II transmembrane glycoprotein that is mainly involved in regulating the differentiation and activation state of the cell. CD38 has broad and complex functions, including enzymatic activity, intercellular signal transduction, cell activation, cytokine production, receptor function and adhesion activity, and it plays an important role in the physiological and pathological processes of many diseases. Many studies have shown that CD38 is related to the occurrence and development of HIV infection, and CD38 may regulate its progression thr

Редкий случай плазмабластической миеломы с двойным Каппой и Lambda mRNA экспрессией, представляющий себя как одинокая тяжёлая опухоль.

Плазмабластическая миелома является агрессивным вариантом миэломы плазменных клеток, которая может имитировать плазмобластную лимфому, когда она представляет собой одиночную массу. Двойное выражение каппы и лямбды светоцепной цепи является исключительно редким и может быть упущено, если оценка основывается только на обнаружении уровня протеина. Мы сообщаем о случае с женщиной в 80 лет, которая подавала опухоль с левым опухолью и перерезала одинокий опухоль и опухоль. Гистология показала, что листы больших плазмбластических клеток являются положительными для CD38, CD138, множественной миэломы о

ЦАРТ клетки в качестве новой терапевтической стратегии для множественных склерозов и других нейроиммунных расстройств.

В качестве трансформационного подхода к лечению множественных склерозов (MS) и других нейроиммунных расстройств, таких, как расстройства спектра нейромиелита (NMOSD), миелин олигодендроцита гликпротеина, связанных с антителами (MOGAD), и миастения гравис (MG), наряду с рядом других редких нейроиммунологических заболеваний, которые в настоящее время оцениваются в исследованиях, посвященных сочувствию или ранней фазе. Отчасти эти условия обусловлены автоматически реактивными клетками B, вызывающими хроническое воспаление и прогрессивное повреждение тканей. Несмотря на то, что нынешняя иммунодуля

Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma.

Surgery with the assistance of conventional radiotherapy, chemotherapy and immunotherapy is the basis for head and neck squamous cell carcinoma (HNSCC) treatment. However, with these treatment modalities, the recurrence and metastasis of tumors remain at a high level. Increasingly, the evidence indicates an excellent anti-tumor effect of chimeric antigen receptor T (CAR-T) cells in hematological malignancy treatment, and this novel immunotherapy has attracted researchers' attention in HNSCC treatment. Although several clinical trials have been conducted, the weak anti-tumor effect and the side

Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases.

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modi

Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients.

Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will high

The complex regulation of TGF-β in cardiovascular disease.

Transforming growth factor β (TGF-β1) is a pleiotropic cytokine with many and complex effects in cell and tissue physiology. This is made possible by a very complex and interwoven signaling system, whose regulation continues to be the focus of a growing line of research. This complex regulation translates to a key role in cardiovascular physiology, hemostasis, and the blood-vessel interface. In accordance with this, the TGF-β1 pathway appears to be deregulated in related disorders, such as atherosclerotic vascular disease and myeloproliferative syndromes. It is expected that the growing amount

Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets.

Cytotoxic CD4+ T lymphocytes are a unique subset of CD4+ T cells characterized by their cytokine secretion and cytolytic activity. Unlike traditional CD4+ helper T cells, cytotoxic CD4+ T lymphocytes exhibit similar cytotoxicity to that of CD8+ T cells, revealing unexpected plasticity in CD4+ T-cell functions. This flexibility suggests that CD4+ T cells can transform and acquire effector functions beyond their conventional functions, emphasizing their importance in various immune responses. Despite the identification of cytotoxic CD4+ T lymphocytes decades ago, recent advancements have broaden