Ask about this productRelated genes to: ULBP1 antibody
- Gene:
- ULBP1 NIH gene
- Name:
- UL16 binding protein 1
- Previous symbol:
- -
- Synonyms:
- RAET1I
- Chromosome:
- 6q25.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-04-27
- Date modifiied:
- 2016-10-05
Related products to: ULBP1 antibody
Related articles to: ULBP1 antibody
- Pancreatic ductal adenocarcinoma (PDAC) often escapes T cell–mediated immunity through impaired major histocompatibility complex class I (MHC-I) antigen presentation, contributing to its limited responsiveness to T cell–based immunotherapies. Because natural killer (NK) cells are capable of eliminating MHC-I–low tumor cells, redirecting NK cytotoxicity represents a promising strategy for these immune-cold tumors such as PDAC. Among activating NK receptors, NKG2D has been widely exploited in NK cell–engaging platforms through the incorporation of NKG2D ligands (MICA/B and ULBP family members). However, the impact of NKG2D ligand (NKG2DL) identity and binding affinity on NK cell engager potency has not been quantitatively defined. - Source: PubMed
Publication date: 2026/03/10
Lee Seul-GiLee MyungjeeLee Hye-MinSon Ga-HyunYoon Sang-RokChae Byeong-HoKim Dae-SeongLee Kyung-MiKim Yong-Sung - High-risk neuroblastoma (NB) often relapses and becomes refractory to treatment, making it a significant contributor to childhood cancer mortality despite its relative rarity. Addressing the challenges posed by NB's resistance to conventional apoptosis-inducing therapies (e.g., chemotherapy and radiation) has become a pressing concern in pediatric oncology research. In recent years, the growing comprehension of alternative cell death modalities distinct from apoptosis has revealed a promising avenue in the endeavor to combat treatment-resistant cancers. One such mechanism, ferroptosis, has attracted increasing attention for its potential role in combating therapy-resistant cancer cells. High-risk NB typically exhibits an immune-excluded phenotype, characterized by minimal immune cell infiltration. Despite this characteristic, the mechanisms underlying immune exclusion and impaired immune activation in NB remain unclear. Here, we demonstrate that the induction of ferroptosis using Erastin, a cystine-glutamate antiporter inhibitor, reduces NB cell proliferation and foci formation. Furthermore, our transcriptomics analysis revealed that treatment with Erastin in NB cells led to increased expression of ULBP1, a ligand to the activating natural killer (NK) cell receptor, NKG2D. Upon ferroptosis induction, the transcription factor ATF4 was found to drive ULBP1 expression in NB cells. Consistent with this, pre-treatment with Erastin sensitized NB cells to NK cell cytotoxicity in co-culture experiments. These results suggest the NK cell's cytotoxic function can be enhanced with Erastin-mediated ferroptosis, which may be beneficial for NB patients. - Source: PubMed
Publication date: 2026/02/10
Anthonydhason VimalaIslamagic ErnaLeijon NikkiGaarder JennieMartinsson TommyFransson SusanneThorén Fredrik BUmapathy Ganesh - Metastatic melanoma is an aggressive malignancy with limited long-term treatment success due to therapeutic resistance and immune evasion. The transient receptor potential melastatin 8 (TRPM8) ion channel is overexpressed in melanoma but its role as therapeutic target remains unexplored. We investigated the anti-tumor effects of novel TRPM8 modulators in metastatic melanoma cells using viability assays, apoptosis markers, mitochondrial function analyses, reactive oxygen species (ROS) measurements and gene silencing. Their functional impact was further assessed in 3D melanoma organoids, clonogenic survival assays, and natural killer (NK) cell co-culture systems. TRPM8 is significantly overexpressed in metastatic melanoma, as compared with the normal counterparts. Its pharmacological inhibition with novel modulators selectively induces calcium-independent mitochondrial apoptosis characterized by ROS accumulation, mitochondrial membrane depolarization, cytochrome c release, and caspase-3 activation. This process involves activation of the ATM/p53 pathway and upregulation of pro-apoptotic proteins. Additionally, TRPM8 modulators increase expression of the NK cell-activating ligand ULBP1, enhancing melanoma susceptibility to NK-mediated cytotoxicity. Our study identifies TRPM8 as a promising biomarker in melanoma. Its targeting triggers mitochondrial cell death and simultaneously boosts NK cell recognition via ULBP1/NKG2D engagement. TRPM8 targeting in combination with immunotherapy might be, hence, further explored in clinical setting of advanced melanoma. - Source: PubMed
Publication date: 2026/02/14
Sorrentino CarmelaLauretta CarmineD'Angiolo RosaMusella SimonaGiovannelli PiaBertamino AlessiaOstacolo CarmineGomez Monterrey IsabelMigliaccio AntimoCastoria GabriellaDi Donato Marzia - High levels of replication stress make cancer cells vulnerable to therapies targeting DNA damage response (DDR) proteins, such as ataxia telangiectasia and Rad3-related (ATR) protein kinase. ATR is a key mediator of the replication stress response and plays a vital role in maintaining genomic stability. This study investigates the immunomodulatory potential of the ATR inhibitor (ATRi) tuvusertib to improve the targeting of prostate cancer (PCa) by immunotherapy. Tuvusertib pretreatment sensitized human PCa cells (DU145 and 22Rv1) to PBMC-derived natural killer (NK)-mediated lysis. Flow cytometric analysis identified upregulation of death receptor tumor-necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), NKG2D ligand ULBP-1, and programmed death-ligand 1 (PD-L1) as a potential immunomodulatory effect of tuvusertib. Enhanced avelumab-mediated antibody-dependent cell-mediated cytotoxicity and lysis by PD-L1 targeting high-affinity NK (PD-L1 t-haNK) cells were observed in tuvusertib-treated DU145. Tuvusertib sensitized cells to lysis by recombinant human TRAIL, and TRAIL signaling blockade reduced NK-mediated lysis of tuvusertib-exposed cells. RNA analysis revealed elevated p21 and reduced Bcl-xL transcript levels in tuvusertib-treated DU145, suggesting an accumulation of DNA damage and suppression of anti-apoptotic signaling, respectively. Pretreatment of NK cells with the interleukin-15 (IL-15) receptor superagonist N-803 (nogapendekin alfa inbakicept) further enhaced the lysis of tuvusertib-exposed cells. In vivo in the DU145 PCa xenograft model, tuvusertib and N-803 combination therapy demonstrated marked and significant antitumor efficacy relative to either monotherapy, eliciting superior tumor growth control and prolonging survival. Our findings support further investigation into the use of ATRi with immune checkpoint blockade and/or immune-stimulating agents in prostate cancer. - Source: PubMed
Publication date: 2025/12/19
Lee Cailyn ASchlom JeffreyHodge James WFabian Kellsye P - Immune-mediated kidney diseases (IMKD) feature microvascular inflammation (MVI), where natural killer (NK) cells act as key effectors. Although cyclosporine A (CsA) is widely used to suppress immune activation in these conditions, its specific effects on NK cells within the renal microenvironment remain poorly defined. This study aimed to clarify how CsA regulates NK-cell function and to explore the role of endothelial cells in this process. Through bulk and single-cell RNA sequencing (RNA-seq) datasets from public repositories, we found that activated NK cells were enriched in glomerular lesions and closely associated with glomerular endothelial cells. Co-culture experiments showed that CsA-pretreated endothelium reduced NK-cell activation and cytotoxicity. Further assays revealed that CsA induced ubiquitination-dependent degradation of endothelial UL16-binding protein 1 (ULBP1), an activating ligand for NKG2D, which in turn weakened NK-cell PI3K/AKT signaling and effector function. These results describe a mechanism linking CsA-induced endothelial changes to NK-cell inhibition. In conclusion, our study demonstrates an endothelium-NK cell axis through which cyclosporin A suppresses immune activation in microvascular inflammation. This mechanism advances current understanding of calcineurin inhibitor action and may guide dosing and the development of endothelial-targeted therapies in IMKD. - Source: PubMed
Publication date: 2025/11/25
Ma JianiYu BingHan XiqiongBao ShengfangLiu ChenxiXu XuemeiHuang HuaWu JingJin Yanliang