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Clinical activity of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, in refractory adult T-Cell leukemia/lymphoma.

GSK-3β is a serine/threonine kinase implicated in tumorigenesis and chemotherapy resistance. GSK-3β blockade downregulates the NF-κB pathway, modulates immune cell PD-1 and tumor cell PD-L1 expression, and increases CD8 + T cell and NK cell function. We report a case of adult T-cell leukemia/lymphoma (ATLL) treated with 9-ING-41, a selective GSK-3β inhibitor in clinical development, who achieved a durable response. A 43-year-old male developed diffuse lymphadenopathy, and biopsy of axillary lymph node showed acute-type ATLL. Peripheral blood flow cytometry revealed a circulating clonal T cell

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… IFN-γ is a key effector cytokine in immunity and upregulates major histocompatibility complex (MHC) molecules and the machinery involved in antigen processing and presentation. 32 This upregulation of cell surface MHC class I by IFN- γ is essential for cytotoxic T cell activation, and thus, the host …

Роль врожденных иммунных клеток в множественном склерозе.

Множественный склероз (MS) — хроническое аутоиммунное, воспалительное и нейродегенеративное заболевание, затрагивающее центральную нервную систему (КНС). MS ассоциируется со сложным взаимодействием между нейродегенеративными и воспалительными процессами, в основном связанными с патогенными Т и В клетками. Однако все большее количество доклинических и клинических данных свидетельствует о том, что врожденный иммунитет играет ключевую роль в поощрении и развитии НР. В этой связи в настоящее время изучаются доклинические и клинические исследования, ориентированные на различные врожденные иммунные

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… Once DCs capture and process pathogens or damage-associated molecular patterns, DCs go through a maturation process, increasing the expression of costimulatory molecules and loading antigen fragments into the major histocompatibility complex (MHC), while they migrate into lymph nodes where they efficiently …

Картирование клеточной этиологии шизофрении и сложных фенотипов мозга.

Психиатрические расстройства являются многофакторными, а эффективные методы лечения отсутствуют. К числу возможных факторов, способствующих решению проблем в области терапевтического развития, относятся сложность человеческого мозга и высокая полигеничность психических расстройств. Сочетание хорошо мощного генома в масштабах всего мозга и анализа генетики и транскриптомики может углубить наше понимание этиологии психических расстройств. Здесь мы используем два важных ресурса для определения типов клеток, связанных с этиологией шизофрении, другими психическими расстройствами и информативным соп

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… We only kept protein-coding genes from the NCBI and removed unexpressed genes, genes with nonunique names and genes in the major histocompatibility complex (MHC) region (chromosome 6, base positions 25000000–34000000). …

Natural Killer Cells in the Malignant Niche of Multiple Myeloma.

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK c

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… During differentiation, NK cells undergo a complex series of educational interactions between major histocompatibility complex type I (MHC-I) molecules and NK surface inhibitory receptors. Thus, they are educated to self-tolerate other healthy cells in the body ( 71 , 72 ). …

Role of T cells and cytokines in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune disease. It causes persistent joint inflammation, aberrant tissue growth, and progressive joint deterioration. T cells have a key role in the onset of RA. They identify and trigger other immune cells, and produce inflammatory signals such as interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Prolonged inflammation and tissue damage are caused by an imbalance between regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) cells. Additionally, the condition is exacerbated by uncontrolled cytokine netwo

Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases.

Osteoarthritis and inflammatory arthropathies are a cause of significant morbidity globally. New research elucidating the metabolic derangements associated with a variety of bone and joint disorders implicates various local and systemic metabolites, which further elucidate the underlying molecular mechanisms associated with these destructive disease processes. In osteoarthritis, atty acid metabolism has been implicated in disease development, both locally and systemically. Several series of rheumatoid arthritis patients have demonstrated overlapping trends related to histidine and glyceric aci

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… RA is a T-cell major histocompatibility complex (MHC) II-mediated immune response against soft tissues, cartilage, and, eventually, bone. …

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immun

Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we describe

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… histocompatibility complex microRNA matrix metalloprotease neutrophils extracellular trap natural killer nitric oxide nitric oxide synthase non‐small cell lung cancer oligodeoxynucleotide programmed cell death protein 1 derived dendritic cell programmed death‐ligand 1 prostaglandin E2 phosphoinositide … When DCs are stimulated and activated, chemokine receptors (such as CCR7), adhesion molecules, costimulatory molecules (CD54, CD80, and CD86), and major histocompatibility complex class I (MHC I) and MHC II molecules are upregulated, leading to a decrease in phagocytic ability and an increased ability …

Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.

Recent advancements in immunotherapy, particularly Chimeric antigen receptor (CAR)-T cell therapy and cancer vaccines, have significantly transformed the treatment landscape for leukemia. CAR-T cell therapy, initially promising in hematologic cancers, faces notable obstacles in solid tumors due to the complex and immunosuppressive tumor microenvironment. Challenges include the heterogeneous immune profiles of tumors, variability in antigen expression, difficulties in therapeutic delivery, T cell exhaustion, and reduced cytotoxic activity at the tumor site. Additionally, the physical barriers w

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… Epitope prediction involves analyzing detected mutations using algorithms that assess their binding affinity to the patient's MHC molecules (major histocompatibility complex), which is essential for T cell recognition. … This structure enables direct recognition of tumor surface antigens without requiring major histocompatibility complex (MHC) presentation. …

Chemotherapy-Induced Tissue Injury: An Insight into the Role of Extracellular Vesicles-Mediated Oxidative Stress Responses.

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to

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… EVs can present cellular peptide antigens on their surface with major histocompatibility complex (MHC) class I and class II molecules. The peptide antigen can activate T-cells directly or indirectly via transferring to antigen-presenting cells. …

Neurological updates: neurological complications of CAR-T therapy.

Chimeric antigen receptor (CAR)-expressing T cells now offer an effective treatment option for people with previously refractory B cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR-T cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR-T cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate ad

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… The intrinsic activation mechanism within CAR-T cells allows them to become fully activated and acquire the full repertoire of effector functions on encountering tumour antigen, without the need for major histocompatibility complex-epitope presentation. …

Urgent considerations on renal immune-related adverse events in oncology practice.

In recent years, immune checkpoint inhibitors (ICIs) have emerged as a critical component of hematological malignancies and solid malignant tumors therapy. However, clinical practice has revealed that these agents may induce immune-related adverse events (irAEs). Notably, renal irAEs stands out as a significant clinical concern, frequently necessitating treatment discontinuation and thereby enabling tumor progression. Renal irAEs constitutes a critical consideration for patients with cancer complicated by chronic kidney disease (CKD). This review systematically examines the immunologic pathoge

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… PD-1, Programmed cell death protein-1; PD-L1, Programmed cell death ligand1; CTLA4, Cytotoxic T lymphocyte-associated antigen-4; TCR, T cell receptor; Treg, regulatory T cell; MHC, Major histocompatibility complex; APC, Antigen-presenting cell; SHP, SH2 domain-containing protein-tyrosine phosphatase. … DC, Dendritic cells; MAC, Membrane attack complex; TCR, T cell receptor; MHC, Major histocompatibility complex. PAMPs, Pathogen-Associated Molecular Patterns. Created in BioRender. lv, w. (2026) https://BioRender.com/sgsw389 . …

Therapeutic Antibodies for Myeloid Neoplasms-Current Developments and Future Directions.

Therapeutic monoclonal antibodies (mAbs) such as antibody-drug conjugates, ligand-receptor antagonists, immune checkpoint inhibitors and bispecific T cell engagers have shown impressive efficacy in the treatment of multiple human cancers. Numerous therapeutic mAbs that have been developed for myeloid neoplasms, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), are currently investigated in clinical trials. Because AML and MDS originate from malignantly transformed hematopoietic stem/progenitor cells-the so-called leukemic stem cells (LSCs) that are highly resistant to

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… Myeloid neoplasms, being cancers of the immune system, express major histocompatibility complex (MHC) class I and II molecules and costimulatory ligands and thereby possess the intrinsic capability to activate T cells ( 186 ). … (A) In secondary lymphoid organs, antigen-presenting cells (APCs) process and present peptides from tumor-derived (neo-)antigens to CD4 + helper T cells (T H cells) via major histocompatibility complex class II (MHC-II) molecules. …

AAV1.NT3 генная терапия смягчает остроту аутоиммунного энцефаломиэлита в модели мыши для множественных склерозов.

Множественный склероз (MS) — хроническое воспалительное и нейродегенеративное заболевание центральной нервной системы (КНС), которое оказывает воздействие более чем на организм человека. 2.5 million Пациенты по всему миру. Хроническое обезвоживание в ЦНС играет важную роль в увековечении аксоновых потерь и увеличивает трудности в поощрении воспоминаний. Поэтому стратегии регенерации и нейрозащиты имеют важное значение для преодоления этого препятствия для сохранения аксоновой целостности и функции. Нейропофин 3 (В тыс.NT-3) обладает иммунодуляционными и антивоспалительными свойствами, помимо ш

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… These migratory cells can present major histocompatibility complex-restricted Ag to CD4 + T cells and CD8 + T cells (cross presentation) and thus play central roles in priming adaptive immune responses. …

Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475) in the management of melanoma and other tumor types.

Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently

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… Abbreviations: MHC, major histocompatibility complex; TCR, T-cell receptor; PD-1, programmed death 1; PD-L1, PD-1 ligand. Pembrolizumab is a humanized PD-1-blocking antibody that blocks the interaction between the PD-1 receptor and its ligands, PD-L1 and PD-L2. …

Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases.

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promi

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… CAR-T therapy and its approval in cancer CAR T cells were first constructed by Eshhar and colleagues in 1989 ( Fig. 1 ), aiming at expressing functional chimeric T cell receptors (TCR) that recognize antigens in a non-major histocompatibility complex (MHC)-restricted manner [ 2 ]. …

CAR T клеточная терапия в неврологических расстройствах, вызванных автоантибиозами: многообещающая стратегия.

Клеточная терапия химерного антигенного рецептора (CAR) Т становится перспективным подходом к неврологическим аутоиммунным расстройствам на базе клеток B, особенно тем, которые характеризуются патогенными автоантиорганизмами, направленными на ключевые нейронные структуры. Эти заболевания, включая расстройство спектрального спектра нейромиелита, миастения гравис, синдром Ламберта-Итона миастеника, болезнь, связанная с антителами MOG, энцефалит рецептора против NMDA, диацилглицирол губазы альфа антитела, ассоциируемый с энцефалитом, синдромом жесткого человека и множественным склерозом, могут бы

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… CAR T cells have the potential to penetrate deeper tissues and are not restricted by major histocompatibility complex (MHC) binding [ 13 , 14 ]. … Histocompatibility Complex Metabotropic Glutamate Receptor 5 Myelin Oligodendrocyte Glycoprotein Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Medical Research Council Multiple Sclerosis Muscle-Specific Tyrosine Kinase N-Methyl-D-Aspartate Receptor Neuromuscular Junction Neuromyelitis …

Клеточные иммунотерапии для множественного склероза: механистические интуиции и клинические достижения.

Множественный склероз (MS) представляет собой хроническое, разнородное, многофакторное, иммунно-дегенеративное заболевание центральной нервной системы, которое влияет на население трудоспособного возраста. На его развитие влияют как генетические, так и экологические факторы. Патологическая характеристика MS - это образование демиелинизирующих повреждений мозга и спинного мозга, которые связаны с нейронными повреждениями, вызванными аутоагрессивными иммунными факторами (Т клетки, В клетки и миэлоидные клетки). Считается, что координационные повреждения вызваны инфильтрацией иммунных клеток в це

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… Unlike CAR-T-cell therapy, which uses artificial chimeric receptors, TCR-T-cell therapy is based on natural mechanisms of antigen recognition in the context of major histocompatibility complex (MHC) molecules [ 145 ] ( Table 1 ). … histocompatibility complex MOG Myelin oligodendrocyte glycoprotein NMOSD Neuromyelitis optica spectrum disorder NSCs Neural stem cells NGF Nerve growth factor PLP Proteolipid protein RRMS Relapsing–remitting multiple sclerosis SLE Systemic lupus erythematosus Tregs regulatory T cells tolDCs Tolerogenic …

Intrinsic retinoic acid synthesis is required for oligodendrocyte progenitor expansion during CNS remyelination.

Myelin regeneration (remyelination) in the CNS depends on the recruitment, proliferation and differentiation of oligodendrocyte precursor cells (OPCs) at demyelinated lesions. However, despite the presence of OPCs, very few oligodendrocytes and myelin are regenerated in chronic multiple sclerosis (MS) lesions for reasons that remain poorly understood. Here, using a spontaneous remyelination model in mice, we found that retinaldehyde dehydrogenase 2 (Raldh2), a rate-limiting enzyme for retinoic acid (RA) synthesis, is upregulated in OPCs and in a subpopulation of microglia/macrophages during re

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… (A) Luxol fast blue staining combined with major histocompatibility complex II peroxidase immunolabeling showing chronic inactive lesion (green square), an active lesion (gray square), perilesion area (yellow highlight) and NAWM (orange square) where quantifications were performed. …

Биомаркеры CSF активации B-клеток в множестве склерозов: клиническая перспектива.

Роль клеток B в патофизиологии множественных склерозов (MS) выходит за рамки синтеза антител, включая также модуляцию T лимфоцитов и миелиоидных клеток. Активация B-клеток в рамках центральной нервной системы связана с высвобождением различных антител, цитокинов и химокинов, которые измеряются в биофильтрах, и тем самым служат биомаркерами иммунных процессов, отвечающих за MS. С этой целью биомаркетная характеристика заболевания посредством сочетания хорошо зарекомендовавших себя маркеров, например, иммуноглобулин (Ig) G-индекс (Ig) G, олиголональные полосы Ig, свободные световые цепи Ig с нов

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… The function of B cells as APCs involved in the induction of EAE was demonstrated in myelin oligodendrocyte glycoprotein (MOG)-induced EAE models, in which the selective knock-out of class II major histocompatibility complex (MHC) on B cells counteracted disease induction [ 38 ]. …