Btla

Hormone receptor-positive breast cancer (HR + BC) is known to be relatively insensitive to chemotherapy, and since chemotherapy has remained the major neoadjuvant therapy for HR + BC, the undetermined mechanism of chemoresistance and how chemotherapy reshapes the immune microenvironment need to be explored by high-throughput technology. By using single-cell RNA sequencing and multiplexed immunofluorescence staining analysis of HR + BC samples (paired pre- and post-neoadjuvant chemotherapy (NAC)), the levels of previously unrecognized immune cell subsets, including CD8+ T cells with pronounced expression of T-cell development (LMNA) and cytotoxicity (FGFBP2) markers, CD4+ T cells characterized by proliferation marker (ATP1B3) expression and macrophages characterized by CD52 expression, were found to be increased post-NAC, which were predictive of chemosensitivity and their antitumor function was also validated with in vitro experiments...

High microsatellite instability (MSI-H) derives from genomic hypermutability due to deficient mismatch repair function. Colorectal (CRC) and endometrial cancers (EC) are the tumor types that more often present MSI-H. Anti-PD(L)-1 antibodies have been demonstrated to be agnostically effective in patients with MSI-H cancer, but 50-60% of them do not respond to single-agent treatment, highlighting the necessity of expanding their treatment opportunities. Ipilimumab (anti-CTLA4) is the only immune checkpoint inhibitor (ICI) non-targeting PD(L)-1 that has been approved so far by the FDA for MSI-H cancer, namely, CRC in combination with nivolumab...

PURPOSE: Immune checkpoint inhibitors (ICI) are then backbone in the therapy of metastatic renal cell carcinoma (RCC). The aim of this analysis was to explore the different expression of the ICI PD-L1, BTLA, and TIM-3 at the different tumor locations of the invasion front and the tumor center. METHODS: Large-area sections of the tumor center and invasion front of 44 stage pT1-4 clear cell RCCs were examined immunohistochemically using antibodies against BTLA, TIM-3, and PD-L1 and subsequently correlated with clinicopathologic data...

Immune checkpoints play a critical role in maintaining the delicate balance of immune activation in order to prevent potential harm caused by excessive activation, autoimmunity, or tissue damage. B and T lymphocyte attenuator (BTLA) is one of crucial checkpoint, regulating stimulatory and inhibitory signals in immune responses. Its interaction with the herpes virus entry mediator (HVEM) plays an essential role in negatively regulating immune responses, thereby preserving immune homeostasis. In cancer, abnormal cells evade immune surveillance by exploiting checkpoints like BTLA...

The CD28-B7 interaction is required to deliver a second signal necessary for T-cell activation. Additional membrane receptors of the CD28 and B7 families are also involved in immune checkpoints that positively or negatively regulate leukocyte activation, in particular T lymphocytes. BTLA is an inhibitory receptor that belongs to a third receptor family. Fish orthologs exist only for some of these genes, and the potential interactions between the corresponding ligands remain mostly unclear. In this work, we focused on the channel catfish (Ictalurus punctatus), a long-standing model for fish immunology, to analyze these co-stimulatory and co-inhibitory receptors...

Head and neck cancer (HNC) is the sixth most common cancer type, accounting for approximately 277,597 deaths worldwide. Recently, the Food and Drug Administration (FDA) has approved immune checkpoint blockade (ICB) agents targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) as a treatment regimen for head and neck squamous cell carcinomas (HNSCC). Studies have reported the role of immune checkpoint inhibitors as targeted therapeutic regimens that unleash the immune response against HNSCC tumors...

BACKGROUND/AIM: Glycolysis has a role in regulating the tumor immune microenvironment. However, the functions and clinical role for facilitating the prognosis prediction of colorectal cancer (CRC) based on glycolysis and immune-related genes remain to be identified. MATERIALS AND METHODS: Genes associated with glycolysis and immunity (GI) were identified from established databases (MSigDB and ImmPort). The TCGA (training cohort) and GSE39582 (validation cohort) datasets were used...

Immune checkpoints secure the proper function of the immune system and the maintenance of the BTLA-HVEM complex, an inhibitory immune checkpoint, is one of the pathways vital for T cell responsiveness to various stimuli. The present study reports the immunomodulatory potential of five peptides targeting the BTLA-HVEM complex on the activity of human T cells. Isolated T cells were exposed to the peptides alone or combined with CD3/CD28 mAb for 72h or 120h. The flow cytometry was used to evaluate the activation markers (CD69, CD62L, CD25), changes within the T-cell memory compartment, proliferation rate, and apoptosis of T cells...

The association between the B and T lymphocyte attenuator ( BTLA ) gene rs1982809 polymorphism and cancer susceptibility has been reported, but these findings are inconsistent. In addition to clarifying the relationship between the rs1982809 polymorphism and cancer susceptibility, the current study also explored the clinical significance of BTLA gene expression. The GSCA tool and Stata software were used to explore the association between BTLA gene expression and tumor stage, immune infiltration, survival prognosis, and drug sensitivity for pan-cancer, and the association of BTLA gene rs1982809 polymorphism with cancer susceptibility, respectively...

Extracellular domain (ECD) antigens are crucial components for antibody discovery, in vitro assays, and epitope mapping during therapeutical antibody development. Oftentimes, those antigens are difficult to produce while retaining the biologic function/activity upon extracellular secretion in commonly used expression systems. We have developed an effective method to cope with the challenge of generating quality antigen ECDs. In this method, a monoclonal antibody (Mab) or antibody fragment antigen-binding (Fab) region acts as a "chaperone" to stabilize the antigen ECD through forming an antibody:antigen complex...

BACKGROUND: The important roles of B7 homologous body 4 ( B7-H4 ), B and T lymphocyte attenuator ( BTLA ) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. METHODOLOGY: Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique...

INTRODUCTION: Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its development at the early phase are highly warranted. METHODS: Here, we analyzed kidneys from healthy mice, diabetic mice, and diabetic mice treated with the sodium-glucose cotransporter 2 inhibitor dapagliflozin using ATAC and RNA sequencing. The findings were verified at the protein levels and in cultured cells...

BACKGROUND: Copper homeostasis and cuproptosis play critical roles in various biological processes of cancer; however, whether they can impact the prognosis of lung adenocarcinoma (LUAD) remain to be fully elucidated. We aimed to adopt these concepts to create and validate a lncRNA signature for LUAD prognostic prediction. METHODS: For this study, the TCGA-LUAD dataset was used as the training cohort, and multiple datasets from the GEO database were pooled as the validation cohort...

BACKGROUND: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group)...

CAR (chimeric antigen receptor) T cell therapy has shown clinical success in treating hematological malignancies, but its treatment of solid tumors has been limited. One major challenge is on-target, off-tumor toxicity, where CAR T cells also damage normal tissues that express the targeted antigen. To reduce this detrimental side-effect, Boolean-logic gates like AND-NOT gates have utilized an inhibitory CAR (iCAR) to specifically curb CAR T cell activity at selected nonmalignant tissue sites. However, the strategy seems inefficient, requiring high levels of iCAR and its target antigen for inhibition...

INTRODUCTION: The effect of platinum-based chemotherapy (Chem.) and second- or multiple- line immune checkpoint PD-1 blocking therapy by Nivolumab or Pembrolizumab (ICI) was assayed in the peripheral blood of non-small cell lung cancer (NSCLC) patients. METHODS: Flow cytometry was used to detect NSCLC-related antigen binding IgG antibodies. The Luminex MagPix multiplex bead-based cytokine/chemokine detecting system was used to quantitatively measure 17 soluble markers in the plasma samples...

BACKGROUND: Follicular lymphoma (FL), the most common indolent non-Hodgkin's Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses. METHODS: To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability...

Esophageal squamous cell carcinoma (ESCC) is a common invasive and pernicious cancer with a low five-year survival rate. To identify potential therapeutic targets, we first investigated the characteristics of cuproptosis genes (CUGs) in ESCC. The expression patterns of 10 CUGs (FDX1, LIPT1, LIAS, DLAT, DLD, PDHA1, PDHB, GLS, MTF1, and CDKN2A) were analyzed to identify ESCC-relevant targets. Weighted correlation network analysis (WGCNA) was performed to obtain CUG-related genes (CRGs). A total of seven differentially expressed genes were identified (FDX1, DLAT, LIAS, PDHB, MTF1, GLS, and CDKN2A)...

This work describes a patient-derived tumoroid model (PDTs) to support precision medicine in lung oncology. The use of human adipose tissue-derived microvasculature and patient-derived peripheral blood mononuclear cells (PBMCs) permits to achieve a physiologically relevant tumor microenvironment. This study involved ten patients at various stages of tumor progression. The vascularized, immune-infiltrated PDT model could be obtained within two weeks, matching the requirements of the therapeutic decision. Histological and transcriptomic analyses confirmed that the main features from the original tumor were reproduced...

BACKGROUND: Immunosuppression is a significant factor contributing to the poor prognosis of cancer. S100P, a member of the S100 protein family, has been implicated in various cancers. However, its role in the tumor microenvironment (TME) of pancreatic cancer remains unclear. This study aimed to investigate the potential impact of S100P on TME characteristics in patients with pancreatic cancer. METHODS: Multiple data (including microarray, RNA-Seq, and scRNA-Seq) were obtained from public databases...