Результаты поиска

Correlation between recognition of autologous tumor organoids by tumor-infiltrating lymphocytes from metastatic epithelial cancers and clinical response.

BACKGROUND: Neoantigen-specific tumor-infiltrating lymphocytes (TILs) have the ability to mediate responses in patients with metastatic epit … (4 patients, 13%), and breast (2 patients, 7%) cancer. RESULTS: Recognition of PDTO was driven by major histocompatibility complex (MHC) class I-restricted reactivity and upregulation of MHC in response to interferon-γ was not associated with response. There were no responders in the 9 patients who lacked PDTO recognition on their initial TIL screening compared with seven respo …

Enhancing Tumor Immunogenicity through Hyaluronic Acid-Mediated Delivery of Nonself Antigenic Peptides.

Tumor-specific cytotoxic T cells (CTLs) recognize and eliminate tumor cells presenting the tumor-associated antigens on major histocompatibility complex (MHC) class I molecules. However, the efficacy of vaccine-induced CTLs is often limited by the low immunogenicity of self-derived tumor antigens. Because the magnitude of an immune response is closely associated with antigen immunogenicity, strategies that enhance the antigenicity of tumor cells can improve the effectiveness of cancer vaccines. In this study, we prepared a series of conjugates consisting of hyaluronic acid (HA), a tumor-target…

IFNγ-dependent tumor-cell MHC-II is restrained by MAPK signaling and associated with immunotherapy responsiveness in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) and poor prognosis. Although major histocompatibility complex class II (MHC-II) is typically expressed by professional antigen-presenting cells, its regulation and significance in malignant PDAC cells remain unclear. Here, we integrated single-cell RNA sequencing, spatial transcriptomics, bulk transcriptomics, multiplex immunohistochemistry, and functional studies in murine PDAC models to investigate tumor-cell MHC-II. Across human PDAC datasets, elevated tumor-cell MHC-II expression w…

Dissemination of T Lymphocytes and Potential Immune-Escape Mechanisms of Bovine Skin Squamous Cell Carcinoma Regarding MHC-1 and PD-L1 Expression.

BACKGROUND: Bovine skin squamous cell carcinoma (SCC) is a malignant neoplasm in cattle triggered by sunlight exposure. Immune escape drives tumour survival and progression. Previous findings in humans have emphasised the prognostic value of immune checkpoint marker (PDL-1), major histocompatibility complex (MHC-1) and cytotoxic CD8 T cells in the context of cancer immune escape. OBJECTIVES: We examined the distribution of CD8+ T cells and the possible immune-escape mechanisms of SCC in relation to PD-L1 and MHC-1 expression and correlated marker expression with tumour grade. ANIMALS: Twenty…

Single-Cell Level Characterization of B Cell Depletion and Repopulation Following Rituximab in Systemic Lupus Erythematosus.

OBJECTIVE: Rituximab, a CD20+ B cell depletion therapy, is frequently used to treat systemic lupus erythematosus (SLE). However, variability … he most changes. Responders specifically had increased expression of genes related to cytotoxicity, major histocompatibility complex class II antigen presentation, and T cell activation in CD4 T central memory and DN T cells. CONCLUSION: Our longitudinal profiling provides single-cell resolution of the shifts in immune cell dynamics following B cell depletion.

HLA-DR risk variants in rheumatoid arthritis: what we know and still do not know.

Rheumatoid arthritis (RA) susceptibility is strongly influenced by genetic variations within the major histocompatibility complex, with HLA-DRB1 risk alleles representing the largest contributors to heritability, particularly in seropositive (anti-citrullinated protein antibody positive) disease. The shared epitope (SE) hypothesis, first proposed more than three decades ago, explained the clustering of susceptibility within HLA-DRB1*04 subtypes. Subsequent fine-mapping expanded HLA-DRB1 disease associations beyond the SE motif, identifying key amino acid residues at positions 11/13, in additio…

T-cell Progenitor-derived Dendritic Cells Contribute to the Repertoire Selection and Immunological Tolerance.

BACKGROUND: Accumulating evidence indicates that bone marrow transplantation induces tolerance against simultaneously transplanted allogenei … ansplantation. RESULTS: Flow cytometric analysis of the ETP culture showed the presence of CD11c + major histocompatibility complex class II + ETP-derived DCs, and the T cells generated in the culture showed a low frequency of specific TCR Vβ repertoire, suggesting clonal deletion. ETP-derived DCs also induced the deletion of a specific Vβ TCR repertoire in the in vitro cocultur …

Modulation of rhesus macaque killer cell immunoglobulin-like receptor-MHC I interactions by simian immunodeficiency virus peptides.

Natural killer (NK) cells are key effectors of innate immunity and contribute to early control of viral infections. Their activity is regulated in part by interactions between killer cell immunoglobulin-like receptors (KIRs) on NK cells and major histocompatibility complex class I (MHC I) molecules on target cells. To investigate how MHC I-bound peptides influence these interactions in the context of simian immunodeficiency virus (SIV) infection of rhesus macaques, we employed ultradense peptide arrays and screened pooled matrices of overlapping peptides to identify sequences presented by comm…

Inherited Disorders and Disease-Resistance Genomics in Kazakhstan Ruminants: Evidence, Limits and Breeding Priorities.

Kazakhstan ruminant genomics is expanding through targeted diagnostic testing, SNP-array studies, whole-genome sequencing, runs of homozygos … is broader but less directly actionable, consisting mainly of prion protein gene preparedness, MHC (Major histocompatibility complex)-related immune hypotheses, reproductive candidate loci, runs of homozygosity, genome wide associated data and pathogen-exposure context. In goats, current evidence is mostly population-genomic and adaptation-oriented, while hereditary-disease surve …

Early-stage 2K1C renovascular hypertension does not increase global MHC-II or F4/80 abundance in the non-clipped kidney but reveals focal F4/80+ induction.

The two-kidney, one-clip (2K1C) model produces renovascular hypertension. The effects on the clipped kidney (CK) are well described, while t … urgery (n = 6). Blood pressure was assessed, and NCKs were collected on day 7. Global expression of major histocompatibility complex (MHC)-II (APC marker) and F4/80 (monocyte/macrophage lineage) was quantified by immunoblotting, while spatial distribution was evaluated by immunohistochemistry (IHC) and morphological analysis. 2K1C produced a significant increase in blood pressure …

Immunoinformatic analysis for identifying immunogenic antigens from the complete proteome of Giardia lamblia.

BACKGROUND: Giardia lamblia is a parasite that infects humans. To date, there is no vaccine available for human giardiasis. Thus, discoverin … WB and GS were submitted to the NetMHCII 2.3 predictor. The analysis was conducted for five murine major histocompatibility complex (MHC)-II molecules: I-Ab, I-Ad, I-Ed, I-Ak, and I-Ek. Python 3.9 was used to develop custom code for data processing and analysis. FINDINGS: We identified 414 potential immunogenic polypeptides for isolate WB and 350 for isolate GS. For both isolat …

Long-term depletion of KIR3DL01+ NK cells by adeno-associated viral-vectored antibody delivery alters chronic SIV infection.

Natural killer (NK) cells are key innate effectors during antiviral immune responses, with their activity regulated in part by interactions between polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex class I (MHC I) ligands on target cells. In human immunodeficiency virus (HIV) infection, certain KIR and MHC I allelic combinations are associated with enhanced viral control and delayed disease progression. To interrogate the contribution of a common KIR+ NK cell subset to the immune response to simian immunodeficiency virus (SIV) i…

ULK1 knockout suppresses pancreatic cancer progression by inhibiting autophagy and enhancing antitumor immunity.

Autophagy plays a dual role in cancer, acting as a tumor suppressor and promoter depending on tumor stage and context. While Atg5 and Atg7 a … essor cells and neutrophils while substantially enhancing recruitment of cytotoxic CD8+ T cells and major histocompatibility complex II+ antigen-presenting cells. Chemokine and cytokine profiling revealed that downregulation of Cxcl2, Ccl2 and G-CSF might lead to polymorphonuclear myeloid-derived suppressor cell and neutrophil recruitment and survival, with concurrent upregulatio …

Genome-wide association studies reveal new insights into the genetic basis of IgG4-related disease in the Chinese Han population.

OBJECTIVES: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder of unknown aetiology, potentially linked to gene … 6 distinct genetic susceptibility loci. The strongest signal mapped to chromosome 6 in the extended major histocompatibility complex region. Notably, chromosome 1 harboured significant loci involving immune-related genes such as the FC-γ receptor gene family. Fine mapping identified 6 independent HLA alleles, 2 amino acid mutations, and SNP rs3888777 as independent significant si …

Революции на передовой линии лечения миеломы: уроки и трудности в поиске лечения.

Множественная миелома (ММ) — рак костного мозга. За последние четверть века был создан заметный комплекс лечебных средств, которые проводят мероприятия по борьбе с миэломой с помощью различных механизмов и обеспечивают долговременную борьбу с болезнями у многих пациентов. Обнаружение того, что протеозные ингибиторы (ИП) и иммуномудуляторные препараты (ИМИД) нацелены на конкретные характеристики плазменных клеток, которые отражают биологию заболеваний и оказывают антимиеломную активность, привело к трансформативным изменениям в алгоритмах лечения. В последнее время появились достижения в област

Совпадение в аннотации оригинала
Multiple myeloma (MM) is a cancer of bone marrow plasma cells. A noteworthy ensemble of therapies has been introduced over the past quarter … and immune cells and trigger a direct tumor-specific cytotoxic response. BsAbs and CAR T-cells are major histocompatibility complex (MHC)-independent approaches to treat MM and do not require T-cell receptor (TCR) specificity. Agents that target BCMA and G protein-coupled receptor class C group 5 member D (GPRC5D) demonstrate impressive clinical responses, while early-phase tria …

Generation of SLA-DQ Knockout Pigs and Screening for Anti-SLA-DQ Antibodies in Sera From Naïve and HLA Class II-sensitized Patients.

BACKGROUND: The most common cause of late graft failure in renal allotransplantation is chronic antibody-mediated rejection caused by donor- … serum suggesting that, like allotransplantation, late xenograft failure may be driven by antidonor major histocompatibility complex class II antibodies, particularly SLA-DQ. Some patients have anti-SLA-DQ antibodies, but the magnitude of this problem is unclear. METHODS: We evaluated patient sera for the presence of anti-SLA-DQ antibodies in engineered immortalized cells, to de …

Single-Agent and Associated Therapies with Monoclonal Antibodies: What About Follicular Lymphoma?

Monoclonal antibodies (mAbs) have become a cornerstone in the treatment of follicular lymphoma (FL), offering highly specific therapeutic ta … notherapeutic strategy, redirecting T-cell activity to eliminate malignant B cells independently of major histocompatibility complex (MHC) antigen presentation. Additionally, antibody-drug conjugates (ADCs) offer a targeted cytotoxic approach by delivering potent chemotherapeutic payloads directly to tumor cells while limiting off-target effects. The integration of mAbs with immu …

Genetic Landscape of Opsoclonus-Myoclonus-Ataxia Syndrome in Children.

BACKGROUND: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neurological disorder, with involuntary rapid saccadic conjugate eye movem … or compound heterozygous variants known to alter protein function, affecting 11 genes. Notably, the major histocompatibility complex, class II, DR beta 1 (HLA-DRB1) ∗01 allele was observed in 27 out of 84 (32.1%) alleles in the patients, significantly higher than that in the general population (chi-square test, P < 0.0001). In one case, a potential genetic modifier of OMAS with s …

Cigarette smoke-primed citrullinated HLA-DR4 T cell reactivity is modulated by γδ-T cells.

OBJECTIVES: Cigarette smoke (CS) increases the risk of seropositive rheumatoid arthritis (RA), particularly in individuals carrying HLA-DR4 (Human Leukocyte Antigen-DR4) shared epitope (SE) alleles, though the underlying mechanisms remain unclear. This study aimed to investigate the interaction between these 2 key risk factors-CS and HLA-DR4-and their effect on T cell responses to citrullinated antigens in early RA and in HLA-DR4 transgenic mice. METHODS: Major histocompatibility complex (MHC)-II tetramer technology was used to detect CD4+ T cells specific for citrullinated antigens in patien…

Clinicopathological profiling and prognosis of idiopathic inflammatory myopathy overlapping with myasthenia gravis: a retrospective cohort study.

BACKGROUND: The clinicopathological spectrum of idiopathic inflammatory myopathy (IIM) overlapping with myasthenia gravis (MG) remains poorl … anti-acetylcholine receptor antibody (AChR-Ab). Muscle biopsies showed CD3+ T cell infiltration and major histocompatibility complex-I expression in all cases. All patients were treated with glucocorticoids plus other immunotherapies. Five patients showed marked improvement, of whom one experienced relapse, and two patients died within 3 months due to severe infection. CONCLUSIO …