PILRα binds an unknown receptor expressed primarily on CD56bright and decidual-NK cells and activates NK cell functions

Ophir, Yael; Duev-Cohen, Alexandra; Yamin, Rachel; Tsukerman, Pinchas; Bauman, Yoav; Gamliel, Moriya; Mandelboim, Ofer

doi:10.18632/oncotarget.8397

Cited by 6 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Supernatants were collected and purified on a HiTrap Protein G HP column in the High Pressure Perfusion Chromatography Station, BioCAD (PerSeptive Biosystems) as previously described. 12 Nectin4-Ig was generated using these primers: Forward primer: GGGG AATT CGCC GCCA CCAT GCCC CTGT CCCT-GGGA Reverse primer: GGGG GATC CGAG GCTG ACAC TAGGTCC. HAVcR-Ig was generated using these primers: Forward primer: GGGA ATTC GCCG CCAC CATG CATC CTCA AGTGGTCA Reverse primer: GGGG ATCC CCTT TAGT GGTA TTGGCCGT.…”

Section: Fusion Proteinsmentioning

confidence: 99%

Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

Reches¹,

Ophir²,

Stein³

et al. 2020

J Immunother Cancer

Self Cite

View full text Add to dashboard Cite

BackgroundThe use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.MethodsWe stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo.ResultsWe identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo.ConclusionWe discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy.

show abstract

Section: Fusion Proteinsmentioning

confidence: 99%

Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

Reches¹,

Ophir²,

Stein³

et al. 2020

J Immunother Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…The PSTPIP1 hub gene was related to T-cell activation, differentiation, and migration, modulating the function of innate immune cells and the innate immune response, and its mutation was confirmed as a crucial driver of immunodeficiency and auto-inflammatory diseases ( Holzinger and Roth, 2016 ; Janssen et al, 2018 ). The PILRA hub gene was primarily expressed on multiple immune cells ( Kogure et al, 2011 ; Sun et al, 2012 ), which can trigger increased natural killer cell–mediated IFN-γ secretion by binding to o-glycosylated receptors ( Ophir et al, 2016 ). However, few studies have reported the correlation between these two protein-coding genes and the tumor-related immune response, and we confirmed that they have a relationship with multiple infiltrating lymphocytes and tumor immune regulation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Prognostic Biomarkers Relevant to Immune Infiltration in Lung Adenocarcinoma

et al. 2022

View full text Add to dashboard Cite

Background: Programmed death ligand-1 (PD-L1) is a biomarker for assessing the immune microenvironment, prognosis, and response to immune checkpoint inhibitors in the clinical treatment of lung adenocarcinoma (LUAD), but it does not work for all patients. This study aims to discover alternative biomarkers.Methods: Public data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to determine the gene modules relevant to tumor immunity. Protein–protein interaction (PPI) network and GO semantic similarity analyses were applied to identify the module hub genes with functional similarities to PD-L1, and we assessed their correlations with immune infiltration, patient prognosis, and immunotherapy response. Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining were used to validate the outcome at the protein level.Results: We identified an immune response–related module, and two hub genes (PSTPIP1 and PILRA) were selected as potential biomarkers with functional similarities to PD-L1. High expression levels of PSTPIP1 and PILRA were associated with longer overall survival and rich immune infiltration in LUAD patients, and both were significantly high in patients who responded to anti–PD-L1 treatment. Compared to PD-L1–negative LUAD tissues, the protein levels of PSTPIP1 and PILRA were relatively increased in the PD-L1–positive tissues, and the expression of PSTPIP1 and PILRA positively correlated with the tumor-infiltrating lymphocytes.Conclusion: We identified PSTPIP1 and PILRA as prognostic biomarkers relevant to immune infiltration in LUAD, and both are associated with the response to anti–PD-L1 treatment.

show abstract

“…As the dominant lymphocyte population in the decidua, decidual NK cells participate in trophoblast invasion and spiral artery remodeling attaining maximum numbers during the first trimester then declining near term (34). Moreover, decidual NK cells play critical roles in promoting anti-viral innate immunity as well as placental development by producing several soluble factors (34)(35)(36)(37)(38). Conversely, lower T cell numbers are present in the first versus third trimester (39).…”

Section: Architecture Of the Maternal-fetal Interfacementioning

confidence: 99%

Vertical Zika Virus Transmission at the Maternal-Fetal Interface

et al. 2022

View full text Add to dashboard Cite

Zika virus (ZIKV) is spread by mosquito bites or via sexual or vertical transmission. ZIKV-infected adults are generally asymptomatic, but can display mild symptoms including fever, joint pain, rash and conjunctivitis. However, during pregnancy, vertical ZIKV transmission can cause placental dysfunction and elicit severe fetal defects, including microcephaly, retinopathy, fetal growth restriction and/or stillbirth. Since no FDA-approved vaccine or anti-viral agents are currently available, ZIKV infection poses a global maternal-fetal health challenge. The maternal-fetal interface consists of maternal decidual and immune cells as well as fetal-derived trophoblasts. Compared to other cell types at the maternal-fetal interface, syncytiotrophoblasts, which form the outer layer of floating villi, are less-permissive to ZIKV, thereby preventing ZIKV transmission to the underlying cytotrophoblasts and/or other cells such as Hofbauer cells or fetal endothelium in the villi. However, anchoring villi are tightly attached to the decidua and their cytotrophoblastic cell columns are ZIKV-permissive, suggesting this location as the most likely site of ZIKV vertical transmission. Thus, at the maternal-fetal interface, maternal decidual cells likely serve as a reservoir of ZIKV persistence since they: 1) overexpress viral entry molecules compared to trophoblasts; 2) are highly permissive to ZIKV infection in a gestational age-dependent manner (more easily infected earlier in gestation); 3) augment ZIKV infection of weakly permissive primary cytotrophoblast cultures; and 4) display local maternal-immune tolerance, which prolongs ZIKV survival to facilitate fetal transmission. This review focuses on molecular mechanisms underlying ZIKV infection of cells at the human maternal-fetal interface, thus highlighting how decidual cells enhance propagation of ZIKV in extravillous cytotrophoblasts and why development of agents that eliminate ZIKV persistence in reproductive tissues before pregnancy is crucial to prevent perinatal ZIKV transmission.

show abstract

PILRα binds an unknown receptor expressed primarily on CD56bright and decidual-NK cells and activates NK cell functions

Cited by 6 publications

References 38 publications

Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

Identification of Novel Prognostic Biomarkers Relevant to Immune Infiltration in Lung Adenocarcinoma

Vertical Zika Virus Transmission at the Maternal-Fetal Interface

Contact Info

Product

Resources

About