The Function of B and T Lymphocyte Attenuator and Its Role in Transplantation

Apmis, Journal Year: 2025, Volume and Issue: 133(3)

Published: March 1, 2025

Immune checkpoints are important molecules that regulate the immune response, preventing its overactivation from causing tissue damage and autoimmune diseases. B T lymphocyte attenuator (BTLA) plays an role in regulating activation suppression of response as part a bidirectional signaling complex. The BTLA ligand herpesvirus entry mediator (HVEM) interaction transmits inhibitory signals suppress biological activity cells, DCs. In addition, BTLA-HVEM can affect induction Treg further suggesting regulation. Organ transplantation is ultimate treatment option for many patients with end-stage organ failure. Transplant rejection cause to transplanted organ, which seriously affects prognosis patients. Therefore, we would like explore potential application value exert immunosuppressive function thus attenuate transplant rejection. We first reviewed structure HVEM, then summarized their research progress transplantation, explored directions future applications challenges current applications.

Language: Английский

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PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 11, 2025

Programmed cell death protein 1 (PD-1) is a critical immune checkpoint receptor and target for cancer inhibitors (ICI). We investigated PD-1 transcript expression across types its correlations to clinical outcomes. Using reference population, was calculated as percentiles in 489 of 514 patients (31 types) with advanced/metastatic disease. RNA varied within types; pancreatic liver/bile duct malignancies displayed the highest rates high (21.82% 21.05%, respectively). Elevated CTLA-4, LAG-3, TIGIT were independently correlated PD-1. Although not associated outcome immunotherapy-naïve (n = 272), who received ICIs 217), prolonged survival (hazard ratio 0.40; 95%CI, 0.18–0.92). This study identifies an important biomarker predicting ICI outcomes, advocates comprehensive immunogenomic profiling management.

Language: Английский

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Immune inhibitory receptor agonist therapeutics

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

The immune system maintains the health of an organism through complex sensing and communication mechanisms. Receptors on surface cells respond to stimuli resulting in activity described at its most basic as inhibitory or stimulatory. Significant progress therapeutic intervention has occurred by modulating these pathways, yet much remains be accomplished. Therapeutics that antagonize, block, receptor (IIR) such checkpoint inhibitors cancer are a key example. Antagonism stimulatory receptors (ISRs) for dysregulated inflammation autoimmunity have received significant attention. An alternative strategy is agonize, induce signaling, pathways treat disease. Agonism ISRs been employed with some success disease settings, but agonist therapeutics IIRs great, untapped potential. This review discusses highlights recent advances pre-clinical clinical designed agonize IIR diseases. In addition, understanding agonists based cellular level either suppression (SuSt), new concept, suppressive (SuSu) proposed.

Language: Английский

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Single-cell sequencing reveals the expansion and diversity of T cell subsets in the bone marrow microenvironment of chronic myeloid leukemia

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101626 - 101626

Published: April 1, 2025

Language: Английский

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Immune checkpoint for pregnancy

Seminars in Immunopathology, Journal Year: 2025, Volume and Issue: 47(1)

Published: May 2, 2025

Language: Английский

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The association of BTLA gene polymorphisms with non-small lung cancer risk in smokers and never-smokers

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 19, 2023

Lung cancer is the predominant cause of death among patients and non-small cell lung (NSCLC) most common type. Cigarette smoking prevailing risk factor for NSCLC, nevertheless, this also diagnosed in never-smokers. B T lymphocyte attenuator (BTLA) belongs to immunological checkpoints which are key regulatory molecules immune response. A growing body evidence highlights important role BTLA cancer. In our previous studies, we showed a significant association between gene variants susceptibility chronic lymphoblastic leukemia renal carcinoma Polish population. The present study aimed analyze impact polymorphic on NSCLC patients' overall survival (OS).Using TaqMan probes genotyped seven single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs9288953, rs1844089, rs11921669 rs2633582 with use ViiA 7 Real-Time PCR System.We found that rs1982809 within associated risk, where carriers rs1982809G allele (AG+GG genotypes) were more frequent compared controls. subgroup analyses, noticed significantly overrepresented never-smokers, but not smokers Additionally, global distribution haplotypes differed never-smokers smokers, G C A, G, never-smoking patients. Furthermore, presence as well rs9288953T (CT+TT increased females' After stratification by histological type, rs2705511C adenocarcinoma Moreover, correlated advanced stages (stage II III), stage IV. rs2705511 modified OS, while rs9288952 tend be survival.Our results indicate may considered low penetrating factors especially females, OS

Language: Английский

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Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12848 - 12848

Published: Nov. 29, 2024

This review explores some of the complex mechanisms underlying antitumor T-cell response, with a specific focus on balance and cross-talk between selected co-stimulatory inhibitory pathways. The tumor microenvironment (TME) fosters both activation exhaustion, dual role influenced by local presence immune checkpoints (ICs), which are exploited cancer cells to evade surveillance. Recent advancements in IC blockade (ICB) therapies have transformed treatment. However, only fraction patients respond favorably, highlighting need for predictive biomarkers combination overcome ICB resistance. A crucial aspect is represented complexity TME, encompasses diverse cell types that either enhance or suppress responses. underscores importance identifying most critical molecules developing approaches tailored patient-specific molecular profiles maximize therapeutic efficacy inhibitors clinical outcomes.

Language: Английский

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Associations between immune cells signatures and osteoarthritis: An integrated analysis of bidirectional Mendelian randomization and Bayesian colocalization

Cytokine, Journal Year: 2024, Volume and Issue: 179, P. 156633 - 156633

Published: May 10, 2024

Language: Английский

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Subset of DN Memory B Cells Expressing Low Levels of Inhibitory Receptor BTLA Is Enriched in SLE Patients

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2063 - 2063

Published: Dec. 13, 2024

The dialogue between T and B cells can be regulated by different mechanisms, such as co-inhibitory receptors, which therefore play a crucial role in preventing autoimmune diseases systemic lupus erythematosus (SLE). lymphocyte attenuator (BTLA) is receptor expressed on many myeloid lymphoid cells. Although peripheral express very high amount of BTLA, previous works the context autoimmunity mainly focused cells, whether BTLA expression plays pathogenesis still unclear. In present study, we examine well its ligand HVEM (Herpesvirus Entry Mediator), various cell subsets patients compared to healthy controls (HCs). We evidenced existence double-negative (DN; IgD−CD27−) memory expressing low levels are enhanced active patients. An in-depth analysis revealed that these BTLAlow DN correspond newly reported DN3 subset, originally described SARS-CoV2 infection. These display an activated antibody-secreting phenotype, propose their may favor expansion rapid differentiation into plasmablasts

Language: Английский

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Blockade of BTLA alone or in combination with PD-1 restores the activation and proliferation of CD8+ T cells during in vitro infection with NCP BVDV

Veterinary Microbiology, Journal Year: 2024, Volume and Issue: 290, P. 110004 - 110004

Published: Jan. 23, 2024

Language: Английский

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