Affinage

PVR

Poliovirus receptor · UniProt P15151

Length
417 aa
Mass
45.3 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PVR (CD155/Necl-5) is an immunoglobulin superfamily cell-surface glycoprotein that serves as a central hub linking cell migration, contact inhibition, and immune regulation. Its extracellular domain engages multiple receptors on NK and T cells — activating DNAM-1 (CD226) and inhibitory TIGIT, CD96, and KIR2DL5 — to bidirectionally tune cytotoxicity, with tumor-derived CD155 driving CD226 internalization and degradation via Src/CBL-B-mediated ubiquitination, thereby promoting immune evasion (PMID:15039383, PMID:19815499, PMID:36377656, PMID:33053330). On non-immune cells, CD155 cooperates with integrin αVβ3 at leading edges to activate Rac/Cdc42 and Akt signaling for directional migration, while nectin-3-induced clathrin-dependent endocytosis of CD155 at cell–cell contacts enforces contact inhibition of proliferation (PMID:14871893, PMID:16216929). CD155 transcription is induced by Ras/Raf-MEK-ERK-AP-1 signaling and by TLR–NF-κB pathways, and its mRNA is post-transcriptionally stabilized by METTL3-dependent m6A modification; its cytoplasmic ITIM domain binds the dynein light chain Tctex-1 to direct CD155-containing vesicles into retrograde microtubule-based transport (PMID:15688018, PMID:23349877, PMID:36860353, PMID:11751937).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Identification of the cytoplasmic Tctex-1 interaction established that CD155 is not merely a passive viral receptor but actively couples to the dynein motor complex for retrograde vesicular transport, revealing a cell-biological function for its intracellular domain.

    Evidence Yeast two-hybrid screen with biochemical pulldown and Co-IP domain mapping in mammalian cells

    PMID:11751937

    Open questions at the time
    • Whether Tctex-1 interaction is required for CD155 trafficking in non-neuronal contexts
    • No structural detail of the CD155-Tctex-1 interface
  2. 2001 Medium

    Demonstration that CD155 binds vitronectin with nanomolar affinity suggested a role in cell–matrix adhesion beyond its known viral receptor function.

    Evidence Surface plasmon resonance quantitative binding assay

    PMID:11437656

    Open questions at the time
    • Limited functional validation in cellular adhesion assays
    • Relationship to integrin αVβ3-dependent migration unclear at this stage
  3. 2003 High

    The discovery that CD155 trans-interacts heterophilically with nectin-3 (but not homophilically) and enhances motility of Ras-transformed cells linked CD155 to intercellular adhesion signaling and oncogenic cell behavior.

    Evidence Binding assays and cell motility assays with trans-interaction partners in NIH3T3 cells

    PMID:12740392

    Open questions at the time
    • Signaling intermediates downstream of the nectin-3–CD155 interaction not yet identified
  4. 2004 High

    Functional identification of CD155 and CD112 as ligands for the activating receptor DNAM-1 on NK and T cells, together with the finding that endothelial CD155–DNAM-1 interaction regulates monocyte diapedesis, established CD155 as a key immunological ligand controlling both cytotoxicity and leukocyte trafficking.

    Evidence Ectopic expression/blocking antibody cytotoxicity assays; soluble DNAM-1-Fc binding on endothelial cells with transendothelial migration readout

    PMID:15039383 PMID:15136589

    Open questions at the time
    • Signaling events downstream of PVR–DNAM-1 engagement in endothelial cells not resolved
    • Relative contributions of CD155 vs. CD112 in vivo unclear
  5. 2004 High

    Showing that CD155 cooperates with integrin αVβ3 at leading edges and activates Rac/Cdc42 for directional migration, while the Tctex-1 interaction mediates retrograde neuronal transport, delineated two distinct signaling modes of CD155 — one extracellular/migratory and one cytoplasmic/trafficking.

    Evidence Mutant CD155 expression in fibroblasts with GTPase activation assays and integrin inhibitors; live-cell vesicle tracking in differentiated PC12 neurons with Tctex-1-binding mutants

    PMID:14871893 PMID:15194795

    Open questions at the time
    • Direct structural basis of CD155–integrin αVβ3 interaction unresolved
    • Whether Cdc42/Rac activation requires integrin kinase activity
  6. 2005 High

    Two advances framed CD155 as an oncogene-responsive, contact-inhibited molecule: Ras/Raf-MEK-ERK-AP-1 signaling was shown to transcriptionally upregulate CD155, and nectin-3-induced clathrin-dependent endocytosis of CD155 at cell–cell contacts was demonstrated to enforce contact inhibition of proliferation and migration.

    Evidence Promoter-reporter assays with AP-1 site mutagenesis and MEK inhibitors; clathrin inhibition with surface expression quantification and proliferation/migration assays

    PMID:15688018 PMID:16216929

    Open questions at the time
    • Endocytic adaptor linking nectin-3 engagement to clathrin machinery not identified
    • Whether AP-1-driven upregulation operates in human tumors in vivo
  7. 2008 Medium

    The finding that CD155's cytoplasmic ITIM is required for enhanced proliferation specifically in Ras-mutant cells, via cyclin D2 upregulation and p27Kip1 downregulation, revealed a cell-intrinsic growth-promoting signaling role for CD155 in oncogenic contexts.

    Evidence CD155 overexpression/knockdown and ITIM deletion mutants in Ras-transformed cell lines with cell cycle analysis

    PMID:17893876

    Open questions at the time
    • Phosphatase recruited by the ITIM in this proliferative context not identified
    • Single lab; not independently replicated
  8. 2009 High

    Discovery of TIGIT as an inhibitory receptor for PVR, functioning through its own ITIM to suppress NK cytotoxicity independently of MHC class I, established PVR as a nexus for balancing activating (DNAM-1) and inhibitory (TIGIT) immune signals.

    Evidence Binding assays, ITIM mutagenesis, NK cytotoxicity assays

    PMID:19815499

    Open questions at the time
    • Relative binding affinities of TIGIT vs. DNAM-1 for PVR not quantitatively resolved in this study
    • Whether TIGIT and DNAM-1 compete for the same PVR epitope
  9. 2012 High

    Two studies expanded CD155's functional scope: CD155 was shown to form a complex with VEGFR2 required for VEGF-induced angiogenesis via Rap1/Akt/eNOS, and HIV-1 Nef was found to downregulate CD155 to evade NK-mediated DNAM-1-dependent lysis, demonstrating pathogen exploitation of the PVR–DNAM-1 axis.

    Evidence Co-IP of CD155–VEGFR2 with siRNA knockdown in HUVECs and Necl-5 KO mouse ischemia model; Nef motif mutagenesis with NK cytotoxicity assays across HIV strains

    PMID:22282193 PMID:22301152

    Open questions at the time
    • Whether CD155 directly contacts VEGFR2 or requires an intermediate
    • Whether other viruses exploit similar CD155 downregulation
  10. 2013 High

    Mechanistic studies on endothelial PVR showed it recruits Shp-2 phosphatase in a Src-dependent manner during monocyte diapedesis, while TLR activation was found to upregulate CD155 on APCs through MYD88/TRIF/NF-κB/IRF3, with CD155-deficient mice showing impaired Th2 differentiation — revealing CD155 as a regulated immunomodulatory ligand.

    Evidence Sequential blocking antibody epistasis with Shp-2 recruitment assays; TLR ligand stimulation in MYD88−/−/TRIF−/− mice with in vivo OVA/CpG immunization

    PMID:23333754 PMID:23349877

    Open questions at the time
    • Whether Shp-2 recruitment is the sole signaling pathway during PVR-mediated diapedesis
    • Mechanism by which CD155 on APCs specifically favors Th2 over other T helper subsets
  11. 2018 High

    Genetic ablation of CD155 in both tumor and host compartments demonstrated dual roles: tumor-intrinsic CD155 promotes growth/metastasis, while host CD155 drives DNAM-1 downregulation on NK and T cells, suppressing anti-tumor immunity. Crystal structure of the CD226–CD155 complex revealed a unique side-by-side IgV arrangement requiring both D1 and D2 of CD226.

    Evidence Cd155−/− mice and CD155-deleted tumor cells in metastasis models; X-ray crystallography of mCD226/hCD155-D1 complex with truncation binding validation

    PMID:29757192 PMID:30591568

    Open questions at the time
    • Structural basis of TIGIT–PVR vs. DNAM-1–PVR competition not resolved
    • Whether tumor-intrinsic CD155 signals through the same ITIM/Akt pathways identified in vitro
  12. 2019 High

    Identification of KIR2DL5 as a fourth immune receptor for PVR — binding a non-overlapping epitope from TIGIT/CD96/DNAM-1 and recruiting SHP-1/SHP-2 to suppress Vav1/ERK/NF-κB — expanded the inhibitory checkpoint network centered on PVR.

    Evidence Binding competition assays, inhibitory synapse imaging, phosphoproteomic analysis, KIR2DL5 blocking mAbs in humanized tumor models

    PMID:36377656

    Open questions at the time
    • Whether KIR2DL5 engagement dominates over TIGIT in specific tissue contexts
    • Structural basis of the non-competitive KIR2DL5 binding mode
  13. 2020 High

    A critical immune evasion mechanism was elucidated: tumor CD155 engagement of CD226 triggers Src-dependent Y319 phosphorylation and CBL-B-mediated ubiquitination/proteasomal degradation of CD226 on CD8+ T and NK cells, explaining why CD226 is lost on tumor-infiltrating lymphocytes and why checkpoint blockade fails. A soluble CD155 isoform preferentially sequesters DNAM-1 over TIGIT to suppress NK killing.

    Evidence CD226 Y319 mutagenesis and CBL-B Co-IP with proteasome inhibitor rescue in vivo; sCD155-expressing tumors in receptor-KO mouse panel with NK degranulation assays

    PMID:32040157 PMID:32591463 PMID:33053330

    Open questions at the time
    • Whether therapeutic CD155 blockade can restore CD226 levels in patients
    • Regulation of the sCD155 splice isoform
  14. 2022 High

    METTL3-mediated m6A modification at specific 3′UTR sites of CD155 mRNA was shown to stabilize the transcript and increase surface CD155 on macrophages, adding a post-transcriptional regulatory layer that links metabolic stress (ox-LDL) to immune checkpoint ligand expression.

    Evidence MeRIP m6A mapping, METTL3 knockdown/overexpression, mRNA stability assays, T cell suppression in humanized mouse model of coronary artery disease

    PMID:36860353

    Open questions at the time
    • Whether m6A-mediated CD155 regulation operates in tumor cells
    • Identity of the m6A reader protein stabilizing CD155 mRNA
  15. 2023 High

    Multiple studies revealed context-dependent regulation: IL-22 from T cells induces CD155 on cancer cells to drive NK dysfunction via CD226 degradation; ER retention of CD155 in giant cell arteritis macrophages expands pathogenic CD96+ T cells; and brain metastasis fibroblasts secrete fucosylated PVR (via HIF1α/FUT11) that remodels cancer cell signaling.

    Evidence Il22−/− and Il22r−/− genetic models with NK assays; subcellular fractionation and humanized GCA mouse model; proteomics/phosphoproteomics of bmCAF secretome with FUT11 knockdown

    PMID:36630913 PMID:37075705 PMID:37995180

    Open questions at the time
    • Whether secreted fucosylated PVR engages the same immune receptors as membrane-bound PVR
    • Mechanism of ER retention in GCA macrophages
    • Whether IL-22-driven CD155 upregulation is targetable therapeutically
  16. 2024 Medium

    Additional transcriptional induction pathways were uncovered: platelet adhesion to circulating tumor cells upregulates CD155 via FAK/JNK/c-Jun to engage TIGIT on NK cells, and PKM2 nuclear translocation driven by METTL1-mediated m7G modification of PKM mRNA activates CD155 transcription through H3K9 lactylation at the CD155 promoter.

    Evidence scRNA-seq with FAK/JNK pathway inhibition and TIGIT antibody blockade in hepatocellular carcinoma; Cut&Run for H3K9la at CD155 promoter with METTL1 KO mice in colorectal cancer

    PMID:38779918 PMID:39741310

    Open questions at the time
    • Whether H3K9 lactylation is a general mechanism across tumor types
    • Single-lab findings for both pathways
    • Relative quantitative contribution of each transcriptional axis to total CD155 levels in tumors

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for how PVR simultaneously engages four distinct receptors (DNAM-1, TIGIT, CD96, KIR2DL5), the identity of the m6A reader stabilizing CD155 mRNA, whether therapeutic CD155 blockade can restore CD226 on tumor-infiltrating lymphocytes in patients, and the relative contribution of membrane-bound vs. soluble vs. secreted fucosylated PVR isoforms to immune evasion in different tumor microenvironments.
  • No co-crystal structure of PVR simultaneously bound to TIGIT and DNAM-1
  • No clinical data on CD155-directed immunotherapy
  • Mechanism of ER retention in disease macrophages uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 3 GO:0005576 extracellular region 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 6 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 4 R-HSA-9609507 Protein localization 2
Partners
CD226CD96DYNLT1ITGB3KDRKIR2DL5NECTIN3TIGIT

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TIGIT binds PVR (CD155) and PVRL2 but not PVRL3, and inhibits human NK cell cytotoxicity directly through its ITIM domain, providing an 'alternative self' mechanism for MHC class I-independent inhibition. Binding assays, ITIM functional analysis, NK cytotoxicity assays Proceedings of the National Academy of Sciences of the United States of America High 19815499
2004 CD155 (PVR) and Nectin-2 (CD112) were identified as the functional ligands for DNAM-1 (CD226); ectopic expression of CD155 on target cells rendered them susceptible to T and NK cell-mediated cytotoxicity in a CD226-dependent manner. Ectopic expression in BW5147 cells, blocking mAb inhibition, cytotoxicity assays, soluble receptor binding affinity measurements International immunology High 15039383
2004 PVR (CD155) is expressed at endothelial cell junctions and interacts with DNAM-1 (CD226) on monocytes to regulate the diapedesis step of transendothelial migration; anti-PVR mAbs arrested monocytes at the apical surface over intercellular junctions. Soluble DNAM-1-Fc binding assay on endothelial cells, blocking mAb treatment in transendothelial migration assay, localization by imaging The Journal of experimental medicine High 15136589
2001 The cytoplasmic domain of CD155 (PVR) associates with Tctex-1, a dynein motor complex light chain, via a SKCSR juxtamembrane motif; this interaction targets CD155-containing endocytic vesicles to the microtubular network for retrograde transport. Yeast two-hybrid screen, biochemical pulldown, co-immunoprecipitation, domain mapping mutagenesis The Journal of biological chemistry High 11751937
2004 CD155/PVR-containing vesicles undergo receptor-dependent endocytosis and retrograde axonal transport; the direct interaction between the cytoplasmic domain of CD155 and Tctex-1 is essential for efficient retrograde transport of poliovirus-containing vesicles along microtubules in neurons. GST pulldown, immunoelectron microscopy, live-cell vesicle tracking in differentiated PC12 cells with wild-type vs. Tctex-1-binding mutant hPVR, vinblastine nerve block in vivo Journal of virology High 15194795
2003 CD155 (Tage4/Necl-5) heterophilically trans-interacts with nectin-3 but not homophilically with itself; this interaction enhances motility of Ras-transformed NIH3T3 cells. Binding assays, cell motility assays with trans-interaction partners, domain analysis The Journal of biological chemistry High 12740392
2004 Necl-5 (CD155/PVR) enhances serum- and PDGF-induced cell migration in an integrin αVβ3-dependent manner; it colocalizes with integrin αVβ3 at leading edges, and its extracellular region is required for directional migration while the cytoplasmic region is required for both directional and random motility. Cdc42 and Rac GTPases are activated downstream. Necl-5 mutant expression in L fibroblasts and NIH3T3 cells, integrin inhibitor/activator assays, dominant-negative Necl-5, co-localization imaging, GTPase activation assays The Journal of biological chemistry High 14871893
2005 Upon cell-cell contact, Necl-5 (CD155/PVR) interaction with nectin-3 triggers clathrin-dependent endocytosis of Necl-5 from the cell surface, reducing cell movement and proliferation—a mechanism underlying contact inhibition. Cell-cell contact assays, clathrin inhibition, surface expression quantification, cell migration and proliferation assays The Journal of cell biology High 16216929
2005 Mouse Necl-5 (CD155/PVR) expression is transcriptionally induced by FGF or oncogenic V12Ki-Ras through the Raf-MEK-ERK-AP-1 signaling pathway; an AP-1 binding site in the Necl-5 promoter is required for this induction. Luciferase reporter assays with Necl-5 promoter, pathway inhibitors (MEK inhibitor), AP-1 site mutagenesis Oncogene High 15688018
2001 CD155 (PVR) specifically binds vitronectin with a Kd of ~72 nM as measured by surface plasmon resonance, mediating cell-to-matrix contacts; related PRR proteins do not show equivalent CD155-like binding. Surface plasmon resonance binding assay, co-localization in lymphoid tissue Virology Medium 11437656
2012 Necl-5 (CD155/PVR) interacts with VEGFR2 and is required for VEGF-induced interaction of integrin αVβ3 with VEGFR2; knockdown of Necl-5 in HUVECs suppresses VEGF-induced Rap1, Akt, and eNOS activation and impairs angiogenic responses in vitro and in vivo. Co-immunoprecipitation, siRNA knockdown in HUVECs, Matrigel tube formation, migration and proliferation assays, Necl-5 knockout mouse hindlimb ischemia model Circulation research High 22282193
2013 During monocyte transendothelial migration, endothelial PVR (CD155) interaction with DNAM-1 recruits tyrosine phosphatase Shp-2 in a Src kinase-dependent manner; this regulates a step in diapedesis between those regulated by PECAM and CD99. PVR resides in the lateral border recycling compartment of endothelial cells. Blocking antibody sequential treatment, Shp-2 recruitment assay, Src kinase inhibition, subcellular fractionation/localization of PVR The American journal of pathology High 23333754
2013 TLR activation upregulates CD155 expression on antigen-presenting cells through MYD88, TRIF, NF-κB, and IRF3 (but not IRF7) signaling; CD155-deficient mice show reduced Th2 differentiation (lower IL-4, fewer GATA-3+ CD4+ T cells) upon immunization. TLR ligand stimulation with pathway inhibitors/knockouts (MYD88-/-, TRIF-/-, NF-κB inhibitors), IRF knockout mice, in vivo immunization with OVA/CpG PloS one Medium 23349877
2012 HIV-1 Nef protein downregulates cell-surface PVR (CD155) on infected T lymphocytes using the same structural motifs used to downregulate HLA-I, reducing total cell-associated PVR; Vpu further optimizes surface PVR reduction. This downregulation abrogates NK-mediated lysis via DNAM-1. Flow cytometry of surface and total PVR levels, Nef motif mutagenesis, NK cytotoxicity blocking assays with anti-DNAM-1 and anti-NKG2D Journal of virology High 22301152
2020 Tumor-derived CD155 initiates phosphorylation of CD226 at tyrosine 319 by Src kinases, enabling ubiquitination of CD226 by CBL-B, followed by internalization and proteasomal degradation of CD226 on CD8+ T cells, thereby driving T cell dysfunction and resistance to immune checkpoint blockade. CD226 Y319 mutagenesis, Src kinase inhibition, CBL-B Co-IP, flow cytometry of CD226 surface levels, proteasome inhibitor rescue, in vivo tumor models with CD226 mutant knock-in Immunity High 33053330
2020 Membrane-bound CD155 on melanoma cells triggers CD226 internalization and degradation on NK cells, resulting in decreased NK-cell-mediated tumor reactivity; IL-15 restores TIGIT and CD226 gene expression on tumor-infiltrating NK cells. Flow cytometry of CD226 surface expression and internalization, in vitro cytotoxicity assays, NK-specific TIGIT deletion in transfer experiments, two mouse melanoma models Clinical cancer research High 32591463
2020 PVRL1 (Nectin-1) on hepatocellular carcinoma cells stabilizes cell-surface PVR protein (without affecting Pvr mRNA), which then interacts with TIGIT on CD8+ effector memory T cells to suppress anti-tumor immunity; knockdown of Pvrl1 reduces surface PVR and decreases tumor growth. shRNA knockdown of Pvrl1 and Pvrl3, surface vs. mRNA PVR measurement, tumor growth assays in vivo, mass cytometry, combination anti-PD1/anti-TIGIT treatment Gastroenterology High 32275969
2018 CD155 loss in tumor cells reduces tumor growth and metastasis through tumor-intrinsic mechanisms; in Cd155-/- mice, DNAM-1 is upregulated and NK and CD8+ T cell effector function is enhanced, demonstrating both cell-intrinsic and immune-extrinsic tumor-suppressive roles. Cd155-/- mouse model, CD155-deleted tumor cells, NK/CD8+ T cell functional assays, DNAM-1 surface expression measurement, in vivo tumor and metastasis models The Journal of clinical investigation High 29757192
2019 PVR/KIR2DL5 is a novel immune checkpoint interaction: KIR2DL5 on NK cells binds PVR without competing with TIGIT, CD96, or DNAM-1; engagement induces inhibitory synapse formation and tyrosine phosphorylation of both ITIM and ITSM of KIR2DL5, recruiting SHP-1 and/or SHP-2 and downregulating Vav1/ERK1/2/p90RSK/NF-κB signaling. Binding competition assays, inhibitory synapse imaging, phosphoproteomic analysis, SHP-1/SHP-2 recruitment assays, KIR2DL5 blocking mAbs, humanized tumor mouse models The Journal of clinical investigation High 36377656
2018 The crystal/structural analysis of CD226 (DNAM-1) bound to CD155 (Necl-5/D1) reveals a unique side-by-side arrangement of two IgV domains of CD226; both D1 and D2 of CD226 interact with CD155-D1, and removal of D2 substantially reduces CD226 binding efficacy to CD155. X-ray crystallography of mCD226-ecto and hybrid mCD226-ecto/hCD155-D1 complex, truncation binding assays Proceedings of the National Academy of Sciences of the United States of America High 30591568
2008 CD155 enhances serum-induced cell proliferation specifically in Ras-mutated cells; the cytoplasmic ITIM of CD155 is required for this effect, and CD155 upregulates cyclin D2 and downregulates p27Kip1 to shorten G0/G1 phase. CD155 overexpression and siRNA knockdown in Ras-transformed and Ras-mutated cancer cell lines, cell cycle analysis, cyclin/CDK inhibitor western blotting, ITIM deletion mutant analysis, FAK inhibitor control International journal of cancer Medium 17893876
2015 CD155 (PVR) mediates a costimulatory signal in CD4+ T cells that promotes Th1 development via NF-κB-induced autocrine IFN-γ and STAT1 positive feedback, independent of IL-12; CD155-deficient mice show attenuated Th1-type contact hypersensitivity. CD155-/- mice, anti-CD155 antibody treatment, cytokine measurement (IFN-γ), Tbx21 expression, NF-κB and STAT1 inhibitor studies, contact hypersensitivity model Journal of immunology Medium 25972481
2020 Soluble CD155 (sCD155), expressed by human tumor cells from a splice isoform lacking the transmembrane region, preferentially binds DNAM-1 over TIGIT and CD96, and inhibits DNAM-1-mediated NK cell degranulation and killing, thereby promoting lung colonization by melanoma cells. In vivo injection of sCD155-expressing vs. parental B16/BL6 melanoma in TIGIT-KO, CD96-KO, and DNAM-1-KO mice; NK depletion experiments; in vitro NK degranulation assays; binding affinity comparison The Journal of experimental medicine High 32040157
2023 T cell-derived IL-22 induces high CD155 expression on cancer cells via IL-22 receptor signaling; excessive CD155 binding to CD226 on NK cells triggers CD226 internalization/degradation and NK cell functional impairment, elevating metastatic burden. Constitutional and T cell-specific Il22 deletion in mouse lung/breast cancer models, Il22 receptor deletion on cancer cells, CD226 surface expression and functional assays, NK cell cytotoxicity assays Immunity High 36630913
2022 In coronary artery disease, macrophage METTL3 overexpression promotes m6A modification at positions 1635 and 3103 in the 3'UTR of CD155 mRNA, stabilizing the transcript and enhancing CD155 surface expression on macrophages, which then deliver inhibitory signals to CD4+ T cells via CD96 and TIGIT. m6A mapping (MeRIP), METTL3 knockdown/overexpression, mRNA stability assays, CD155 surface and mRNA measurements, T cell suppression assays in vitro and humanized mouse model Nature cardiovascular research High 36860353
2023 In giant cell arteritis, macrophages retain CD155 in the endoplasmic reticulum and fail to translocate it to the cell surface; CD155low antigen-presenting cells expand CD4+CD96+ T cells that release IL-9, driving vasculitis. CD155 subcellular fractionation/localization in GCA vs. control macrophages, CD4+CD96+ T cell expansion assays, recombinant IL-9 administration and anti-IL-9 antibody treatment in humanized mouse model of GCA Cell reports. Medicine Medium 37075705
2010 Necl-5 (CD155/PVR) knockdown in glioblastoma cells reduces invasion in 3D matrix and decreases MMP-2 expression and activity; Necl-5 activates Akt (which drives MMP-2 expression) through integrin-linked kinase (ILK) at focal contacts, where Necl-5, Akt, and ILK co-localize. RNAi knockdown, 3D invasion assay, MMP-2 zymography, western blotting for Akt activation, co-localization imaging Journal of neuro-oncology Medium 20680398
2020 Bone marrow stromal cell-derived IL-8 upregulates PVR (CD155) surface expression on multiple myeloma cells at the transcriptional level via NF-κB; CXCR1/2 blockade or IL-8 RNA interference prevents PVR upregulation, and stromal microvesicles carrying IL-8 are required for the effect. Dominant-negative IκBα overexpression, CXCR1/2 blocking, IL-8 RNAi, NF-κB reporter assays, microvesicle isolation and functional assays, NK cytotoxicity assays Cancers Medium 32069911
2021 In cervical cancer cells, CD155 physically interacts with AKT and activates the AKT/mTOR/NF-κB pathway to inhibit autophagy and apoptosis; AKT knockdown reverses these effects, establishing CD155 as an upstream regulator of AKT. Co-immunoprecipitation of CD155 and AKT, CD155 KD/OE, AKT knockdown rescue experiments, western blotting for mTOR/NF-κB pathway components, autophagy/apoptosis assays Frontiers in oncology Medium 34164340
2024 Platelet adhesion to circulating tumor cells transcriptionally upregulates CD155 via FAK/JNK/c-Jun cascade; CD155 on CTCs then engages TIGIT (but not CD96 or DNAM-1) on NK cells to inhibit cytotoxicity and promote metastasis. scRNA-seq, multiplex immunofluorescence, in vitro/ex vivo/in vivo cytotoxicity assays, FAK/JNK pathway inhibition, competition binding assays, TIGIT antibody blockade Hepatology Medium 38779918
2024 METTL1-mediated m7G modification of PKM mRNA enhances PKM2 expression, promoting glycolysis and H3K9 lactylation; PKM2 nuclear translocation then transcriptionally activates CD155 expression in colorectal cancer cells, creating a positive feedback loop that promotes immune evasion. RIP assay for m7G-PKM interaction, RNA stability analysis, ChIP (Cut&Run) for H3K9la at CD155 promoter, siRNA knockdown, METTL1 KO mice, western blotting Journal of translational medicine Medium 39741310
2007 PVR (CD155) is constitutively expressed in osteoclast precursors and stromal cells; soluble DNAM-1 extracellular domain (which binds PVR) inhibits multinucleated osteoclast formation specifically at the fusion step (days 6–7), and this suppression is partially abrogated by PVR-specific siRNA. PVR expression profiling in osteoclastogenesis stages, soluble DNAM-1-Fc treatment, PVR siRNA knockdown rescue Molecular and cellular biochemistry Medium 17286202
2023 Brain metastasis cancer-associated fibroblasts (bmCAFs) secrete fucosylated PVR (CD155); HIF1α transcriptionally upregulates fucosyltransferase 11, which fucosylates PVR and triggers its secretion; secreted fucosylated PVR modulates cell-cell junction and actin cytoskeletal signaling in breast cancer cells to enhance invasion. Proteomics of bmCAF conditioned medium, HIF1α ChIP, FUT11 knockdown, global phosphoproteomics of cancer cells treated with PVR, functional invasion assays Cell reports Medium 37995180

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America 718 19815499
2001 Overexpression of the CD155 gene in human colorectal carcinoma. Gut 242 11454801
2004 Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). International immunology 226 15039383
2004 DNAM-1 and PVR regulate monocyte migration through endothelial junctions. The Journal of experimental medicine 219 15136589
2022 TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy. Journal for immunotherapy of cancer 174 35379739
2009 DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. Journal of immunology (Baltimore, Md. : 1950) 159 20008292
2018 Targeting PVR (CD155) and its receptors in anti-tumor therapy. Cellular & molecular immunology 147 30275538
2020 Hepatocellular Carcinoma Cells Up-regulate PVRL1, Stabilizing PVR and Inhibiting the Cytotoxic T-Cell Response via TIGIT to Mediate Tumor Resistance to PD1 Inhibitors in Mice. Gastroenterology 145 32275969
2020 IL15 Stimulation with TIGIT Blockade Reverses CD155-mediated NK-Cell Dysfunction in Melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 131 32591463
2015 Clinical significance of CD155 expression in human pancreatic cancer. Anticancer research 131 25862891
2020 CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8+ T Cells. Immunity 129 33053330
2022 Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer. Journal for immunotherapy of cancer 120 36104099
2001 Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis. The Journal of biological chemistry 115 11751937
2003 Tage4/Nectin-like molecule-5 heterophilically trans-interacts with cell adhesion molecule Nectin-3 and enhances cell migration. The Journal of biological chemistry 114 12740392
2019 Tumor intrinsic and extrinsic immune functions of CD155. Seminars in cancer biology 111 31883911
2012 The human immunodeficiency virus type 1 Nef and Vpu proteins downregulate the natural killer cell-activating ligand PVR. Journal of virology 110 22301152
2004 Poliovirus receptor CD155-targeted oncolysis of glioma. Neuro-oncology 105 15279713
2018 CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. The Journal of clinical investigation 94 29757192
2004 Receptor (CD155)-dependent endocytosis of poliovirus and retrograde axonal transport of the endosome. Journal of virology 94 15194795
2005 Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 with nectin-3. The Journal of cell biology 90 16216929
2004 Nectin-like molecule-5/Tage4 enhances cell migration in an integrin-dependent, Nectin-3-independent manner. The Journal of biological chemistry 87 14871893
2020 Tumor CD155 Expression Is Associated with Resistance to Anti-PD1 Immunotherapy in Metastatic Melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 85 32345648
2020 CD155 immunoregulation as a target for natural killer cell immunotherapy in glioblastoma. Journal of hematology & oncology 84 32532329
2019 A brief review of the histopathology of proliferative vitreoretinopathy (PVR). Eye (London, England) 82 31792351
2020 Tumor-derived soluble CD155 inhibits DNAM-1-mediated antitumor activity of natural killer cells. The Journal of experimental medicine 76 32040157
2019 Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer. Oncoimmunology 75 31741778
2001 The poliovirus receptor CD155 mediates cell-to-matrix contacts by specifically binding to vitronectin. Virology 74 11437656
2019 A Platform for Extracellular Interactome Discovery Identifies Novel Functional Binding Partners for the Immune Receptors B7-H3/CD276 and PVR/CD155. Molecular & cellular proteomics : MCP 73 31308249
2023 T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis. Immunity 71 36630913
2022 Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer. Journal of translational medicine 69 35729552
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2007 The adhesion receptor CD155 determines the magnitude of humoral immune responses against orally ingested antigens. European journal of immunology 61 17621371
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2021 Asynchronous blockade of PD-L1 and CD155 by polymeric nanoparticles inhibits triple-negative breast cancer progression and metastasis. Biomaterials 60 34186238
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2013 Poliovirus receptor (CD155) regulates a step in transendothelial migration between PECAM and CD99. The American journal of pathology 58 23333754
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2021 TIGIT/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells. Oral oncology 49 34333450
2004 PVF1/PVR signaling and apoptosis promotes the rotation and dorsal closure of the Drosophila male terminalia. The International journal of developmental biology 47 15602694
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2014 Pvr expression regulators in equilibrium signal control and maintenance of Drosophila blood progenitors. eLife 45 25201876
2024 The immune checkpoint TIGIT/CD155 promotes the exhaustion of CD8 + T cells in TNBC through glucose metabolic reprogramming mediated by PI3K/AKT/mTOR signaling. Cell communication and signaling : CCS 44 38216949
2012 Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis. Circulation research 44 22282193
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2020 Combination of PD-L1 and PVR determines sensitivity to PD-1 blockade. JCI insight 41 32554931
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2013 Inhibition of PVR with a tyrosine kinase inhibitor, dasatinib, in the swine. Investigative ophthalmology & visual science 39 23341014
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2010 Inhibition of Necl-5 (CD155/PVR) reduces glioblastoma dispersal and decreases MMP-2 expression and activity. Journal of neuro-oncology 27 20680398
2022 Engineering of immune checkpoints B7-H3 and CD155 enhances immune compatibility of MHC-I-/- iPSCs for β cell replacement. Cell reports 26 36170817
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2024 Hemin blocks TIGIT/PVR interaction and induces ferroptosis to elicit synergistic effects of cancer immunotherapy. Science China. Life sciences 25 38324132
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2018 CD155 downregulation synergizes with adriamycin to induce breast cancer cell apoptosis. Apoptosis : an international journal on programmed cell death 25 30039180
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2024 IL-22 signaling promotes sorafenib resistance in hepatocellular carcinoma via STAT3/CD155 signaling axis. Frontiers in immunology 16 38596684
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2018 The bispecific anti-CD3 × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer. Investigational new drugs 14 30374653
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2007 Expression and possible role of PVR/CD155/Necl-5 in osteoclastogenesis. Molecular and cellular biochemistry 12 17286202