Ask about this productRelated genes to: ULBP1 Blocking Peptide
- 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 Blocking Peptide
Related articles to: ULBP1 Blocking Peptide
- KRAS mutation drives oncogenic progression and creates an immunosuppressive microenvironment in cancers like pancreatic ductal adenocarcinoma and colorectal cancer. We investigate the immunomodulatory mechanisms of the KRAS inhibition and its synergy with natural killer (NK) cell therapies. We demonstrate that KRAS inhibition with MRTX1133 remodels the immune landscape by reducing myeloid-derived suppressor cell (MDSC) accumulation and facilitating infiltration and activation of NK and CD8 T cells. Crucially, MRTX1133 reverses systemic immunosuppression, restoring the fitness of adoptively transferred NK cells. Mechanistically, KRAS inhibition impairs IFNGR1 palmitoylation and subsequent lysosomal degradation. MRTX1133 stabilizes IFNGR1 by reducing palmitoyltransferase expression and the palmitate pool. This stabilization increases IFN-γ/IFNGR signaling and up-regulates NK cell-activating ligands ICAM1 and ULBP1, thereby sensitizing cancer cells to NK cells. Consequently, combining MRTX1133 with IL-15 or adoptive NK cell therapy yields synergistic antitumor responses and prolonged survival. Our findings provide mechanistic rationale for combining KRAS inhibitors with NK cell-based immunotherapies to improve outcomes for patients with KRAS-mutant cancers. - Source: PubMed
Publication date: 2026/07/23
Hu TuoMo TaiweiWang LinKe QiuqingChi LiangjieChen HongyuanXu ChaoHuang ChenshenLin AipingCai ShaoxinChen HaiyuWang WenyuJin LongyangZhao JunzhangLiu HaoyunLiu ChuanyuanBaihetiyaer YimamuTuersun AbudumaimaitijiangAbulimiti AbuduhalikeZheng YanWang ZuweiChen ShiCao JieLu ShiyunHuang XuepingXue FangqinHe Chunbo - TB meningitis (TBM) has up to 50% mortality in people living with HIV. We investigated differences in cerebrospinal fluid (CSF) host immune responses associated with short-term mortality. - Source: PubMed
Publication date: 2026/06/18
Louine MartineauDandekar RaviReddy Sumanth PKaralius Mary CWaldrop GreerWang ShiyinGakuru JaneKimuda SarahMugabi TimothyMusubire Abdu KKagimu EnockAbassi MahsaKabahubya MableWilliams Darlisha APhan Hoang VanDai BiyueZia MahamZorn Kelsey CFouassier CamilleGerungan ChloeMarra Pedro SSkipper Caleb PBahr Nathan CLangelier Charles RCreswell Fiona VBoulware David RMeya David BWilson Michael R - Neuroblastoma (NB) is the most common extracranial solid tumor in children and remains a major therapeutic challenge in high-risk patients because of frequent recurrence and metastasis. γδT cells are a unique lymphocyte subset with potent antitumor activity and are widely distributed in NB tumors. However, the immunosuppressive tumor microenvironment limits γδT-cell effector function and promotes immune evasion. In this study, we found that ULBP1 expression was frequently down-regulated in NB tumor tissues and cell lines and that low ULBP1 expression was associated with high-risk clinical features and poor prognosis. Further investigation revealed that doxorubicin, a key chemotherapeutic agent used in NB treatment, up-regulated ULBP1 through down-regulating DNA methyltransferase 1 (DNMT1), thereby decreasing methylation of the ULBP1 promoter. This epigenetic modulation sensitized NB tumor cells to γδT-cell-mediated cytotoxicity in vitro and in vivo. Collectively, our findings uncover a novel mechanism by which doxorubicin enhances NB tumor susceptibility to γδT-cell-mediated killing through ULBP1 up-regulation. This study provides a strong rationale for combining chemotherapy with γδT-cell-based immunotherapy to improve outcomes in high-risk NB patients. - Source: PubMed
Wang HuiWang XiaolinYang WeiWang WeiChai WenjiaLiu XiangjunFeng JunYang ShenSong WenqiLi QiliangZhang HuiMou WenjunChen XiPei MengmiaoLu ZhengjingPeng YunSu YanYao XingfengWang HuanminGui Jingang - Cell targeting/permeabilization, organelle/biochemical pathway regulation, and drug resistance/metastasis/immunological expressions are considerations to advance cancer nanomedicine design. This study modulated mitochondria-targeting YKWYYRGAA (P1) peptide, into a multifunctional excipient via N-methylation and N-dimethylation, to synergise nano-chitosan conjugate in drug delivery and non-small cell lung cancer treatment. The spray-dried chitosan nanoparticles developed from P1, N-methylated YKWYYRGAA (P2) and N-dimethylated YKWYYRGAA (P3) were subjected to physicochemical testing, NRAS-mutated H1299 cell permeability/cytotoxicity/apoptosis and cell cycle arrest/drug resistance/metastasis/immunomodulation assessment, and in vivo pharmacokinetics/pharmacodynamics investigations. Methylated P2 increased cancer cell permeability/intracellular drug/nanoparticle uptake/drug targeting via sustained- and pH-stimuli responsive release and cytotoxicity unlike P1 and P3 which were ceased at membrane interface by excessive ionic/hydrophobic interactions. P2-grafted nanochitosan induced mitochondria-mediated apoptosis with minimal necrosis via ROS activation and FasL-linked death. It suppressed mTOR/MAPK signalling overcoming EGFR-resistance/EGFR mutation-independent pathways in tumorigenesis. It mitigated drug resistance via downregulating P-gp (efflux receptor) and GSTP1 (degrading enzyme) expressions, and epithelial-mesenchymal transition via interplay of E-cadherin against N-cadherin/snail/twist 1/vimentin/ezrin/MMP9 with MICA/ULBP1 suppression to reduce immunological lung tissue lysis. The inhaled P2-grafted nanochitosan provided a positive lung cancer recovery with reduced systemic exposure and hematological/biochemical toxicities. Single instead of dimethylation of YKWYYRGAA promoted the cascades of inter-dependent anti-cancer activities and efficacy of nanochitosan. - Source: PubMed
Publication date: 2026/05/10
Zaiki YazidChee Chin FeiAgeitos LuciaNaharudin IdanawatiZainudin Badrul HisyamLeong Lek MunJaime Rodriguez GonzálezJimenez CarlosGan Chee YuenTraini DanielaWong Tin Wui - Intestinal barrier (IB) dysfunction contributes to metabolic endotoxemia and associated diseases. Specifically, intestinal inflammation upregulates natural killer cell receptor 2D ligands (NKG2DLs) in intestinal epithelial cells (IECs), which triggers excessive immune responses and exacerbates IB injury. The prebiotic xylooligosaccharides (XOS) hold promise for ameliorating such injury by regulating NKG2DLs, yet the underlying mechanisms remain elusive. This study aimed to investigate the efficacy of XOS in improving IB injury and explore its role and molecular mechanisms in mitigating IB damage via NKG2DLs modulation. IB injury models were established in differentiated Caco-2 and MODE-K cells by treatment with 20 ng/mL tumor necrosis factor-α (TNF-α), followed by XOS intervention at concentrations of 50, 100, 150, and 200 μg/mL. Tight junction (TJ) proteins (ZO-1, Occludin) were detected using Western blotting (WB) and immunofluorescence, while barrier permeability was evaluated via transepithelial electrical resistance (TEER), phenol red permeability assay, and transmission electron microscopy (TEM). Additionally, the RhoA/ROCK/MLCK signaling pathway, apoptosis-related factors (Caspase-3, Bcl-2), and the expression of human NKG2DLs (MICA, MICB, ULBP-1) and murine NKG2DLs (Rae-1ε, H60, MULT-1) were analyzed by quantitative real-time PCR (qRT-PCR) or WB, and apoptotic cells were labeled using the TUNEL assay. To further investigate the involvement of NKG2DLs in the protective effect of XOS, RNA interference (RNAi) was performed to knock down NKG2DLs in Caco-2 and MODE-K cells. This conserved mechanism relies on Argonaute (Ago) family proteins that associate with small RNAs to mediate sequence-specific degradation of complementary target RNAs. Subsequently, both cell lines were treated with TNF-α and XOS, and the expression levels of NKG2DLs, ZO-1, and Occludin were determined by qRT-PCR or WB. Compared with TNF-α treatment alone, XOS at the concentrations used in this study significantly attenuated the downregulation and mislocalization of ZO-1 and Occludin in both Caco-2 and MODE-K cells (p < 0.05), increased TEER in Caco-2 cell (p < 0.05), reduced phenol red permeability (p < 0.05), and improved the ultrastructure of TJs and the integrity of microvilli. XOS at the tested concentrations also inhibited the activation of the RhoA/ROCK/MLCK signaling pathway (p < 0.05), suppressed Caspase-3 (p < 0.05) and the number of TUNEL-positive apoptotic cells, and alleviated TNF-α-induced overexpression of both human and murine NKG2DLs (p < 0.05). Notably, RNAi-mediated knockdown of Rae-1ε or H60 in MODE-K cells abrogated the XOS-induced restoration of ZO-1 and Occludin expression under TNF-α challenge. Collectively, under the experimental conditions of this study, XOS mitigate IB injury by inhibiting apoptosis, RhoA/ROCK/MLCK signaling and NKG2DLs in IECs. - Source: PubMed
Publication date: 2026/04/26
Yang JunyiGuo LeiRen ShijingLai QiuyuYang ShunyuWu YanhuaYing ShihaoMeng YitingLi Qing