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Эпигенетика и метаболическая метаболическая дисфункция при многоразовом склерозе: обзор подходов к травяным лекарствам и текущих клинических испытаний.

Множественный склероз (MS) — сложная аутоиммунная болезнь, характеризующаяся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (КНС). Хотя точные причины остаются неясными, недавние исследования подчеркивают важную роль эпигенетических изменений и митохондриальной дисфункции в начале и развитии болезни. Эпигенетические изменения, такие, как метилация ДНК, модификация гистона и регулирование микроРНК, влияют на генное выражение, не изменяя последовательности ДНК, что приводит к иммунной дисрегуляции и воспалению. Аналогичным образом, митохондриальная дисфункция, отме

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… Histone deacetylases (HDACs), such as HDAC1, have the ability to inhibit the expression of major histocompatibility complex (MHC) genes, including HLA-DR, a crucial allele associated with multiple sclerosis. … The importance of the major histocompatibility complex (MHC) in MS patients is highlighted by this dynamic. …

Помимо CAR-T: Предотвращение и лечение релапса в гематологических злодеяниях B-Cell.

Цимерическая антигенная лейкемия (КАР) Т-клетотерапия произвела революцию в области лечения рентгеновской/рефракторной (R/R) острой лимфоболической лейкемии (B-LAL), неходгкинской лимфомы (NHL) и множественной миеломы (MM); однако значительная часть пациентов в конечном итоге, несмотря на первоначальные ответные меры, вновь заболела. В настоящем обзоре содержится краткий обзор клеточной терапии CAR-T, включая ее производственный процесс и связанные с этим токсичные свойства, до изучения биологических механизмов, лежащих в основе рецидива после CAR-T в B-ALL, NHL-особенно большой лимфомы B-клет

Single-cell sequencing technology to characterize stem T-cell subpopulations in acute T-lymphoblastic leukemia and the role of stem T-cells in the disease process.

BackgroundPrecursor T-cell acute lymphoblastic leukemia (Pre-T ALL) is a malignant neoplastic disease in which T-cells proliferate in the bone marrow. Single-cell sequencing technology could identify characteristic cell types, facilitating the study of the therapeutic mechanisms in Pre-T ALL.MethodsThe single-cell sequencing data (scRNA-seq) of Pre-T ALL were obtained from public databases. Key immune cell subpopulations involved in the progression of Pre-T ALL were identified by clustering and annotating the cellular data using AUCell. Next, pseudo-temporal analysis was performed to identify

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… CD74 is a type II transmembrane glycoprotein involved in the regulation of antigen presentation, formation of major histocompatibility complex class II proteins, and B-cell maturation and survival. …

New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia.

Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohor

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… CARs, recombinant surface proteins consisting of antigen-binding and T-cell-activating domains, can direct T cells to lyse malignant cells independently of the major histocompatibility complex ( 6 ). …

Гены второго класса HLA связаны с множественным склерозом: иммуногенетическое прогнозирование среди многих склерозов иорданских пациентов.

Множественный склероз (MS) — вспыльчивая аутоиммунная болезнь, затрагивающая центральную нервную систему (КНС). Патогенез MS характеризуется нейронной аксонной дегенерацией и демиэлизацией. Среди генов, которые повышают риск склероза, есть гены второго класса HLA. Цель этого исследования заключалась в изучении роли генов HLA-DRB1 и HLA-DQB1 ( впервые) в иорданских пациентах, больных MS, и их связи с заболеваниями MS. Были исследованы связи этих генов с другими клиническими особенностями, такими, как оптический неврит, сенсорное расстройство и симптомы сетчатки головного мозга у пациентов MS, а

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… Numerous studies have reported that there are genetic association between MS and major histocompatibility complex (MHC) genes, such as class II Human Leukocyte Antigen (HLA)-DR alleles being of great interest [ 5 – 7 ]. …

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA

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… Elotuzumab has ben used to arm an anti-CD3 (OKT3) antibody to develop a bispecific antibody-armed activated T cell to induce adaptive cellular and humoral immune responses in MM patients, to mediate MM cytotoxicity independently from major histocompatibility complex. … histocompatibility complex. | Short half-life and they need continuous infusion Multiple dosing is expected to elicit a durable response, with intermittent infusions (usually every 3 weeks) CAR-T cells | A virus-free CAR gene transfer using advanced Sleeping Beauty (SB) transposon technology. …

A novel NKG2A alpaca nanobody targeting immune checkpoint blockade for the treatment of malignant melanoma.

Alpacas belong to the Camelidae family. Antibodies produced through alpaca immunization are called nanoantibodies. Compared to traditional antibodies, nanoantibodies have several characteristics, including smaller molecular weight, stable structure, high homology with human antibodies, and suitability for prokaryotic expression. Malignant melanoma (MM) is a severe and aggressive form of cancer that affects both humans and animals. It commonly arises in the mucous membranes of the skin, nose, mouth, anus, and digestive tract, as well as in the choroid of the eyes. Multiple factors contribute to

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… On the surface of human immune cells, the heterodimer complex NKG2A-CD94, formed by the NKG2A and CD94 molecules linked by disulfide bonds, recognizes the nonclassical major histocompatibility complex class I (MHC I) molecule HLA-E on target cells. …

Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

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… histocompatibility complex class I; NK, natural killer; PD-L1, programmed death-ligand 1; TAMs, tumor-associated macrophages; TGF, transforming growth factor; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand; VEGF, vascular endothelial growth factor Cytokine | Antitumor mechanisms … IFN family IFN-α up-regulates major histocompatibility complex (MHC) class I molecule expression on tumor cells, enhances tumor immunogenicity, and induces tumor cell cycle arrest and apoptosis [ 103 ]. …

Modulating CD8⁺ T cell immunity through exercise: mechanistic insights and implications for precision immunotherapy.

CD8⁺ T lymphocytes are pivotal effectors of adaptive immunity, executing cytotoxic mechanisms essential for pathogen clearance, tumor surveillance and tissue protection. Their activity is shaped by antigenic stimulation, cytokine networks and the metabolic and structural architecture of the tissue microenvironment. Physical exercise has emerged as a potent, non-pharmacological modulator of CD8⁺ T cell biology, capable of influencing recruitment, activation, differentiation and functional persistence. Acute exercise mobilizes effector and memory subsets, enhances trafficking to peripheral tissu

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… Upon recognition of antigenic peptides presented by MHC (Major histocompatibility complex) class I molecules, naïve CD8⁺ T cells undergo clonal expansion and acquire effector functions, including the secretion of perforin and granzymes to induce target-cell apoptosis, and the production of pro-inflammatory … Abbreviations Major histocompatibility complex Forkhead box p3 C-X-C motif chemokine receptor 3 C-C motif chemokine receptor 5 Intercellular adhesion molecule 1 Vascular cell adhesion molecule 1 extracellular vesicles Effector memory pancreatic ductal adenocarcinoma Vascular endothelial growth …

The expression and role of miR-181a in multiple myeloma.

This study aims to investigate the role of miR-181a in multiple myeloma (MM). Fresh peripheral blood and bone marrows were collected. Expression of miR-181a, BCL-2 mRNA, and NOVA1 mRNA was detected by RT-qPCR. The correlation between miR-181a and clinical features of MM was further analyzed. miR-181a in serum and bone marrow mononuclear cells of MM patients were significantly higher. And, miR-181a level was significantly higher in MM Durie-Salmon stage III than that in stage I+II. miR-181a was positively correlated to Durie-Salmon staging, age, kidney injury, bone injury, β2-MG whereas negativ

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of C

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… The CAR expressing T cells attach to a specific antigen on cancer cells in an MHC (Major Histocompatibility Complex) independent fashion and are better equipped to specifically target the tumor. The structure of CAR-T cells consists of an ectodomain, a transmembrane domain, and an endodomain. … (A) T-cell activation and stimulatory checkpoints - The first signal for T-cell activation is provided by the binding of T Cell Receptor (TCR) with the antigen (Ag) presented by the Antigen Presenting Cell (APC) in the context of Major Histocompatibility Complex (MHC). …

Lymphoma in Border Collies: Genome-Wide Association and Pedigree Analysis.

There has been considerable interest in studying cancer in dogs and its potential as a model system for humans. One area of research has been the search for genetic risk variants in canine lymphoma, which is amongst the most common canine cancers. Previous studies have focused on a limited number of breeds, but none have included Border Collies. The aims of this study were to identify relationships between Border Collie lymphoma cases through an extensive pedigree investigation and to utilise relationship information to conduct genome-wide association study (GWAS) analyses to identify risk reg

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… DLA-79 is a Major Histocompatibility Complex (MHC) class Ib gene and is thought to play a special role in the immune response, likely binding a distinct set of peptides or ligands [ 72 ]. DLA-79 has 64% amino acid identity with the consensus sequence of HLA-A , -B, and -C . …

Gut microbiota shapes cancer immunotherapy responses.

The gut microbiota significantly influences cancer immunotherapy efficacy by modulating immune responses, remodeling the tumor microenvironment (TME), and producing key metabolites. Strategies such as FMT, probiotics, and dietary interventions show promise in enhancing responses to ICIs and ACTs while reducing immune-related adverse events (irAEs). This review summarizes clinical and preclinical findings and discusses microbiota-based interventions and future directions for precision immunotherapy.

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… DC, dendritic cell; MHC-I, major histocompatibility complex class I; MHC-II, major histocompatibility complex class II; TCR, T cell receptor; PRR, pattern recognition receptor; NK, natural killer; CTL, cytotoxic T lymphocyte. … DC, dendritic cell; MHC-I, major histocompatibility complex class I; MHC-II, major histocompatibility complex class II; TCR, T cell receptor; PRR, pattern recognition receptor; NK, natural killer; CTL, cytotoxic T lymphocyte. …

Integrated Engineering of CAR-T Cells for Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has achieved durable efficacy in hematologic malignancies but encounters persistent obstacles in solid tumours, including antigen heterogeneity, a suppressive tumour microenvironment (TME), and intrinsic T-cell dysfunction. This review examines the transition from single-axis engineering to an integrated framework that addresses these hurdles in sequence. We delineate how next-generation CAR-T cells are designed for precise spatiotemporal activation through logic-gated and pharmacologically regulatable receptors, while being reinforced by metaboli

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… Drawing inspiration from physiological T cell activation—where APCs provide necessary primary (peptide—major histocompatibility complex (MHC)/TCR) and costimulatory (CD80/86‐CD28) signals—this platform integrates activation moieties directly onto the nanoparticle surface. … Co‐expression of TAPi and class II transactivator (CIITA)‐targeted shRNA to downregulate major histocompatibility complex (MHC) I/II reduced immunogenicity and the risk of host rejection—an important consideration given documented anti‐CAR responses after repeated dosing—and expands the potential utility …

Case Report: Primed dendritic cell immunotherapy for multiple solid tumors.

Many patients with advanced solid tumors ultimately develop resistance to conventional therapies, with especially limited options for those experiencing rapid progression or poor performance status, highlighting the need for personalized immunotherapies capable of inducing durable responses. In this retrospective case series, we describe the clinical course and outcomes of five adults (4 male, 1 female; median age 51 years [range, 39-62]) with metastatic solid tumors who achieved complete and durable remission following doubly loaded autologous dendritic cell therapy after failure of standard

30 Years of Improved Survival in Non-Transplant-Eligible Newly Diagnosed Multiple Myeloma.

The treatment of multiple myeloma (MM) has greatly evolved these past few years. Recent advances in therapeutics have largely benefited elderly patients now renamed "non-transplant-eligible" (NTE) patients. Since the 1960s, and for several decades, chemotherapy was the only treatment for MM. Then, the field was marked by the emergence of targeted therapies in the 2000s, such as immunomodulating agents (thalidomide, lenalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), which were the first steps towards an increase in survival. Thereafter, the appari

MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.

Homozygous deletion of the 9p21.3 genomic locus spanning the CDKN2A/B and MTAP genes is an event affecting 15% of cancers. While CDKN2A is a well-established tumor suppressor gene, the role of MTAP in tumorigenesis varies across cancer types. MTAP codes for methylthioadenosine phosphorylase, a key enzyme in the methionine salvage pathway, and its loss has been associated with several downstream synthetic vulnerabilities. Despite multiple efforts to exploit MTAP loss for targeted therapies, none of these efforts have yielded substantial results in clinical trials. In this review, we consolidate

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… In another study involving mouse models of liver HCC tumors, PRMT5 inhibition promoted lymphocyte infiltration and induced major histocompatibility complex II (MHC II) expression in the tumor microenvironment [ 172 ]. … histocompatibility complex II MLPA | Multiplex ligation-dependent probe amplification MMP | Matrix metalloproteinase MPM | Malignant pleural mesothelioma MTA | Methylthioadenosine MTAP | Methylthioadenosine phosphorylase mTOR | Mammalian target of rapamycin MTR-1-P | 5-methylthioribose-1-phosphate NF-κB …

Cordycepin Sensitizes Cholangiocarcinoma Cells to Be Killed by Natural Killer-92 (NK-92) Cells.

Immunotherapy harnessing immune functions is a promising strategy for cancer treatment. Tumor sensitization is one approach to enhance tumor cell susceptibility to immune cell cytotoxicity that can be used in combination with immunotherapy to achieve therapeutic efficiency. Cordycepin, a bioactive compound that can be extracted from some Cordyceps spp. has been reported to effectively inhibit tumor growth, however, the mechanism of its tumor sensitization activity that enhances immune cell cytotoxicity is unknown. In the present study, we investigated the potency of cordycepin to sensitize a l

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… The major histocompatibility complex class I chain related-protein A (MICA) and B (MICB) act as activation ligands, which are plentifully expressed on various carcinomas and can interact with natural killer group 2D receptors (NKG2D), thus triggering the cytolytic responses of NK cells and eventuating …

Balancing Quality, Cost, and Access During Delivery of Newer Cellular and Immunotherapy Treatments.

Purpose of reviewThe chimeric antigen receptor (CAR) T-cell therapy is currently changing the landscape of hematologic malignancies with multiple FDA-approved cell therapy products in the USA. The current administration process of the CAR T-cell therapy is complicated, labor-intensive, and expensive.Recent findingsThe chimeric antigen receptor (CAR) T-cell therapy is currently changing the landscape of hematologic malignancies with multiple FDA-approved cell therapy products in the USA. The current administration process of the CAR T-cell therapy is complicated, labor-intensive, and expensive.

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… To overcome these issues, scientists have tried to incorporate more intense lymphodepletion chemotherapy or genetic modification to remove donor major histocompatibility complex [ 42 ]. …

Потеря ADAP1/CentA1 защищает от аутоиммунной демиэлизации.

ArfGAP с двойным PH-содержащим домен белком 1 (ADAP1), также известным как Centaurin альфа-1 (CentA1) — связующий белок, ярко выраженный в центральной нервной системе (CNS), который ранее, как было показано, регулировал плотность и пластичность позвоночника. В контексте болезни ADAP1/CentA1 связана с болезнью Альцгеймера (AD) патогенезом, развитием рака и активацией вируса иммунодефицита человека (ВИЧ). Здесь мы документируем, что ADAP1/CentA1 также механистически участвует в CNS автоиммунитет. Мы показываем, что мыши с дефектами ADAP1/CentA1 демонстрируют частичное сопротивление разработке эк

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… Consistently, Ly6c ‐high monocytes from CentA1 ‐null mice exhibit downregulation in the major histocompatibility complex II (MHCII) genes H2‐Aa , H2‐Ab1 , and H2‐Eb1 . Lastly, the NK cell population is another immune cell subset that appears to be affected by the lack of ADAP1/CentA1. …