Affinage

TIGIT

T-cell immunoreceptor with Ig and ITIM domains · UniProt Q495A1

Length
244 aa
Mass
26.3 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TIGIT (VSTM3) is a CD28-family inhibitory immune checkpoint receptor that restrains T cell, NK cell, and innate lymphoid responses by competing with the activating receptor CD226 for the shared nectin ligands CD155 and CD112, forming a CD28/CTLA-4-like regulatory network in which soluble TIGIT attenuates T cell responses and TIGIT-deficient animals become more susceptible to autoimmunity (PMID:21416464). TIGIT engages CD226 in cis to disrupt CD226 dimerization and co-stimulation, but it also signals cell-intrinsically: upon CD155 ligation it reorganizes into dense nanoclusters that coalesce with TCR clusters at the immune synapse and, through its phosphorylated ITT-like motif, recruits SHIP-1 to inhibit NF-κB and ERK activation and suppress cytokine secretion independently of CD226 (PMID:25465800, PMID:37596248, PMID:35729552). This receptor binds multiple nectin-family ligands beyond CD155, including nectin-4 with weaker affinity, all converging on inhibition of lymphocyte cytotoxicity (PMID:37542773). In NK cells TIGIT acts as a distinct checkpoint whose blockade reverses exhaustion and enhances tumor immunity and ADCC-driven responses, while also contributing to NK cell education through CD155-dependent functional maturation (PMID:29915296, PMID:28438433, PMID:28623459). Beyond cytotoxic effectors, TIGIT controls CD4+ T cell fate by limiting CD28-driven PI3K/AKT/mTOR co-stimulation, glucose oxidation, and acetyl-CoA-dependent histone acetylation, thereby restraining Th1/Th17 differentiation (PMID:40374622), and it triggers activation-induced cell death of ILC2s upon CD155 engagement to limit allergic inflammation (PMID:37036426). TIGIT is also exploited for immune evasion: the Fusobacterium nucleatum Fap2 protein directly binds human TIGIT to suppress NK and T cell activity in tumors (PMID:25680274).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2011 High

    Established TIGIT as an inhibitory CD28-family receptor by defining its ligands and demonstrating that its loss enhances autoimmune susceptibility, placing it in a CD28/CTLA-4-like regulatory network.

    Evidence Ligand binding assays, soluble protein treatment, and VSTM3 knockout mice under autoimmune challenge

    PMID:21416464

    Open questions at the time
    • Did not define the intracellular signaling mechanism
    • Cis vs trans ligand engagement not distinguished
  2. 2014 High

    Showed that TIGIT inhibits T cells not only by ligand competition but by physically disrupting CD226 dimerization in cis, and that combined TIGIT/PD-L1 blockade synergistically restores CD8+ effector function.

    Evidence Co-IP for cis interaction, CD226 dimerization assays, and in vivo tumor and chronic viral infection blockade models

    PMID:25465800

    Open questions at the time
    • Relative contribution of cis-disruption versus cell-intrinsic signaling not resolved
    • Did not address contexts where CD226 is absent
  3. 2015 High

    Revealed a pathogen-driven immune evasion route by showing Fusobacterium nucleatum Fap2 directly engages human TIGIT to suppress NK and T cell antitumor activity.

    Evidence F. nucleatum mutant library screen, direct protein interaction assay, and NK cytotoxicity assays

    PMID:25680274

    Open questions at the time
    • Fap2 does not bind mouse TIGIT, limiting in vivo modeling
    • Downstream signaling triggered by Fap2 not mapped
  4. 2017 High

    Demonstrated that TIGIT contributes to NK cell education and missing-self recognition via CD155, defining a developmental role distinct from MHC-I and CD226 pathways, and that TIGIT is induced on activated CD16+ NK cells.

    Evidence CD155-deficient mouse models, NK education and missing-self recognition assays, and ADCC blockade experiments

    PMID:28438433 PMID:28623459

    Open questions at the time
    • Molecular signaling underlying education not defined
    • How TIGIT discriminates education versus inhibition unresolved
  5. 2018 High

    Identified TIGIT as a checkpoint in NK cells distinct from PD-1 and CTLA-4 whose blockade prevents NK exhaustion and enhances anti-PD-L1 therapy.

    Evidence TIGIT blockade in multiple tumor models with NK depletion controls and exhaustion marker analysis

    PMID:29915296

    Open questions at the time
    • Intracellular signaling driving NK exhaustion not detailed
    • Translation to human NK cells not directly tested here
  6. 2020 High

    Showed TIGIT limits immunopathology by inducing IL-10 and modulating T cell cytokine profiles during viral infection without affecting virus control, separating its tolerogenic role from antiviral clearance.

    Evidence TIGIT modulation in influenza and chronic LCMV mouse models with cytokine and organ pathology readouts

    PMID:32152316

    Open questions at the time
    • Cellular source and induction mechanism of IL-10 not fully resolved
    • Whether IL-10 mediates protection causally not isolated
  7. 2022 Medium

    Defined the cell-intrinsic inhibitory signaling axis by showing CD155-engaged, phosphorylated TIGIT recruits SHIP-1 to suppress NF-κB and ERK and reduce cytokine output in CD8+ T cells.

    Evidence Western blotting of NF-κB/ERK components and TIGIT blockade in activated CD8+ T cells with in vivo validation

    PMID:35729552

    Open questions at the time
    • Direct physical SHIP-1 recruitment to the ITT motif not structurally demonstrated
    • Single-lab finding with limited mechanistic depth
  8. 2022 High

    Provided structural and affinity definition of the TIGIT-PVR interface via an anti-TIGIT antibody, linking interface blockade to enhanced NK killing and reduced Treg suppression.

    Evidence Crystal structure of MG1131 scFv-TIGIT complex, SPR affinity, and NK/Treg functional assays

    PMID:35090381

    Open questions at the time
    • Structure of native TIGIT-ligand engagement at the synapse not captured
    • In vivo efficacy of the antibody not reported here
  9. 2023 High

    Established that TIGIT signals cell-intrinsically through ITT-motif-dependent nanocluster formation at the immune synapse to inhibit cytokine secretion independently of CD226, likely the dominant mechanism in tumors where CD226 co-expression is rare.

    Evidence Super-resolution microscopy, ITT-motif mutagenesis, and matched tumor/blood lymphocyte cytokine analysis

    PMID:37596248

    Open questions at the time
    • Proximal kinases phosphorylating the ITT motif not all defined
    • Quantitative balance between cis-CD226 and intrinsic signaling in vivo unresolved
  10. 2023 High

    Broadened the TIGIT ligand repertoire by demonstrating recognition of the membrane-distal nectin-4 ectodomain, a weaker interaction than nectin-2 that still inhibits NK cytotoxicity.

    Evidence SPR biophysics, structure-guided mutagenesis of the binding interface, and NK cytotoxicity assays

    PMID:37542773

    Open questions at the time
    • Physiological contexts where nectin-4 engagement dominates not defined
    • In vivo relevance of the weak interaction untested
  11. 2023 High

    Defined a metabolic-epigenetic mechanism by which TIGIT restrains CD4+ T cell pathology, limiting CD28-driven PI3K/AKT/mTOR signaling, glucose oxidation, acetyl-CoA production, and histone-acetylation-dependent Th1/Th17 differentiation.

    Evidence TIGIT knockout EAM mice, T cell differentiation and metabolic assays, histone acetylation analysis, and overexpression rescue

    PMID:40374622

    Open questions at the time
    • Direct link between TIGIT signaling and the metabolic switch not fully traced
    • Which histone marks and loci are reprogrammed not exhaustively mapped
  12. 2023 High

    Revealed a pro-apoptotic role for TIGIT in innate lymphocytes, showing CD155 on macrophages drives activation-induced cell death of TIGIT+ ILC2s to limit chronic allergic inflammation.

    Evidence TIGIT lineage-tracer and knockout mice, anti-TIGIT blockade, macrophage co-culture, and chromatin accessibility analysis

    PMID:37036426

    Open questions at the time
    • Signaling pathway from TIGIT to AICD not delineated
    • Whether this AICD mechanism operates in other lymphocyte lineages unknown
  13. 2024 High

    Showed that TIGIT, but not CD96 or CD226, mediates CD155-dependent suppression of NK surveillance of circulating tumor cells, with platelet-induced CD155 upregulation via FAK/JNK/c-Jun.

    Evidence Receptor-specific competition and cytotoxicity assays, pathway western blotting, and in vivo metastasis models

    PMID:38779918

    Open questions at the time
    • Receptor selectivity mechanism over CD96 not explained
    • Contribution to metastasis in patients not established
  14. 2023 Medium

    Extended TIGIT function beyond classical lymphocytes by implicating it in B cell suppression of Tfh cells, macrophage polarization, and renal injury, broadening its cellular reach.

    Evidence B cell/cTfh co-culture with axis blockade and TCF4 analysis, anti-TIGIT macrophage repolarization and phagocytosis assays, and TIGIT-knockout AKI mouse models with scRNA-seq

    PMID:36250467 PMID:36549780 PMID:36747315

    Open questions at the time
    • Cell-intrinsic versus extrinsic effects in non-T/NK lineages not fully separated
    • Single-lab findings for each context
  15. 2018 Medium

    Identified an upstream regulatory layer controlling TIGIT abundance, showing the lncRNA MEG3 sponges miR-23a to raise TIGIT expression and suppress Th1/Th17 differentiation.

    Evidence MEG3 overexpression, miR-23a sponging assay, and TIGIT expression measurement in an aplastic anemia mouse model

    PMID:30382432

    Open questions at the time
    • Direct miR-23a binding to TIGIT transcript not confirmed
    • Single-lab finding in one disease model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TIGIT integrates its multiple modes of action — cis-CD226 disruption, ITT/SHIP-1 intrinsic signaling, ligand-specific affinities, and metabolic-epigenetic control — into a quantitative hierarchy across cell types and disease contexts remains unresolved.
  • No unified model weighting cis versus intrinsic signaling in vivo
  • Proximal kinase(s) for the ITT motif not fully defined
  • Ligand-selectivity rules across the nectin family incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 2
Partners
CD112CD155CD226FAP2NECTIN-4SHIP-1

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 The Fap2 protein of Fusobacterium nucleatum directly binds human TIGIT (but not mouse TIGIT), leading to inhibition of NK cell cytotoxicity and T cell activity, identifying a bacterium-dependent tumor immune evasion mechanism via TIGIT. F. nucleatum mutant library screen, direct protein interaction assay, NK cell cytotoxicity assay Immunity High 25680274
2014 TIGIT directly interacts with CD226 (DNAM-1) in cis on T cells, disrupting CD226 dimerization and thereby inhibiting CD226-mediated co-stimulation; antibody co-blockade of TIGIT and PD-L1 synergistically enhances CD8+ T cell effector function in tumor and chronic viral infection models. Co-IP for cis interaction, antibody blockade in vivo tumor and viral infection models, CD226 dimerization assay Cancer cell High 25465800
2018 TIGIT is expressed on NK cells and its blockade prevents NK cell exhaustion, promotes NK cell-dependent tumor immunity, and enhances anti-PD-L1 therapy; TIGIT constitutes a checkpoint in NK cells distinct from CTLA-4 and PD-1. TIGIT blockade antibody in tumor-bearing mouse models, flow cytometry for NK exhaustion markers, in vivo tumor rechallenge Nature immunology High 29915296
2011 VSTM3/TIGIT is a CD28 family member whose ligands are CD155 and CD112 (also ligands for activating receptor CD226), forming a regulatory network analogous to CD28/CTLA-4/CD80/CD86; soluble VSTM3 attenuates T cell responses in vitro and in vivo, and VSTM3-deficient mice are more susceptible to autoimmune challenges. Ligand binding assays, soluble protein treatment in vitro and in vivo, VSTM3 knockout mice with autoimmune challenge European journal of immunology High 21416464
2023 TIGIT ligation by CD155 causes TIGIT to reorganize into dense nanoclusters at immune synapses that coalesce with TCR-rich clusters; this directly inhibits T cell cytokine secretion via TIGIT's intracellular ITT-like signalling motif, independently of CD226 co-inhibition. TIGIT and CD226 co-expression is rare on tumor-infiltrating lymphocytes, making this cell-intrinsic signalling mechanism likely dominant in tumors. Super-resolution microscopy, matched tumor/blood lymphocyte analysis, ITT-motif mutagenesis, cytokine secretion assays Nature communications High 37596248
2022 TIGIT, upon binding to CD155 and being phosphorylated, inhibits NF-κB and ERK activation by recruiting SHIP-1, resulting in downregulation of cytokine production in CD8+ T cells; blocking TIGIT attenuates SHIP-1 inhibitory effect and restores NF-κB and ERK activation. Western blotting for NF-κB and ERK pathway components, TIGIT blockade in activated CD8+ T cells, in vivo antibody blockade Journal of translational medicine Medium 35729552
2017 TIGIT engagement by CD155 on NK cells contributes to NK cell education/functional maturation: TIGIT+ NK cells from CD155-deficient hosts show functional impairment, and TIGIT deficiency impairs NK cell-mediated missing-self recognition and rejection of CD155-negative targets in an MHC-I-independent and CD226-unrelated manner. TIGIT+ NK cell isolation, CD155-deficient mouse model, NK cell education assays, missing-self recognition assays Journal of autoimmunity High 28438433
2017 All PVR-like receptors are expressed on human NK cells, with TIGIT preferentially expressed on the CD16+ NK cell subset; TIGIT is upregulated upon NK cell activation via ADCC, and blockade of TIGIT or CD112R (separately or together) enhances trastuzumab-triggered antitumor NK cell responses. Flow cytometry for receptor expression, ADCC assays, antibody blockade of TIGIT and CD112R Cancer immunology, immunotherapy : CII Medium 28623459
2022 Crystal structure of anti-TIGIT monoclonal antibody MG1131 (scFv version) bound to TIGIT reveals the PVR-binding interface; MG1131 binds TIGIT more tightly than PVR and blocks the PVR-TIGIT interaction, inhibiting immunosuppressive signaling, enhancing NK cell tumor killing, and inhibiting Treg suppressive activity. Crystal structure determination, SPR binding assays, NK cell cytotoxicity assays, Treg functional assays mAbs High 35090381
2023 Biophysical experiments demonstrate TIGIT recognizes the membrane-distal ectodomain of nectin-4; structure-guided mutagenesis maps the nectin-4 binding interface on TIGIT; the TIGIT:nectin-4 interaction is weaker than the well-characterized TIGIT:nectin-2 interaction and inhibits NK cell cytotoxicity. Surface plasmon resonance, structure-guided mutagenesis, NK cell cytotoxicity assay Biochemical and biophysical research communications High 37542773
2023 Mouse TIGIT interacts with and is inhibited by mPVR only (not by other nectin ligands); TIGIT-deficient mice generated by CRISPR-Cas9 show enhanced NK cell cytotoxicity and degranulation against tumors in vitro and slower in vivo tumor progression compared to wild-type mice. CRISPR-Cas9 knockout mice, ligand interaction assays, NK cell cytotoxicity/degranulation assays, in vivo tumor growth models Oncoimmunology High 37261087
2023 TIGIT deficiency in CD4+ T cells promotes their differentiation into Th1 and Th17 cells via enhanced CD28-mediated PI3K/AKT/mTOR co-stimulatory pathway, promoting glucose oxidation, citrate production, and increased cytosolic acetyl-CoA levels, leading to epigenetic reprogramming via histone acetylation; TIGIT overexpression rescues this phenotype, and pharmacological histone acetylation inhibition suppresses Th1/Th17 differentiation. TIGIT knockout mouse model (EAM), CD4+ T cell differentiation assays, metabolic measurements, histone acetylation analysis, TIGIT overexpression rescue experiments Nature communications High 40374622
2023 TIGIT mediates activation-induced cell death (AICD) of ILC2s during chronic airway allergy; CD155 expressed on macrophages enhances cell death in TIGIT+ ILC2s via TIGIT engagement; genetic ablation of Tigit or anti-TIGIT antagonistic antibodies promote ILC2 survival and worsen chronic allergic inflammation. TIGIT lineage tracer mice, Tigit genetic ablation, anti-TIGIT antibody blockade, chromatin accessibility analysis, co-culture with macrophages The Journal of experimental medicine High 37036426
2022 TIGIT blockade in AML shifts polarization of TIGIT+ M2 leukemia-associated macrophages toward the M1 phenotype, increases secretion of M1-associated cytokines, and augments anti-CD47-mediated phagocytosis of AML cells in vitro. Anti-TIGIT antibody blockade of primary LAMs and monocyte-derived M2 macrophages in vitro, cytokine profiling, phagocytosis assays Journal for immunotherapy of cancer Medium 36549780
2024 CD155 on CTCs (circulating tumor cells) inhibits NK-cell cytotoxicity specifically through engagement with TIGIT (but not CD96 or DNAM-1/CD226); platelet adhesion to CTCs upregulates CD155 transcriptionally via the FAK/JNK/c-Jun cascade, and TIGIT antibody blockade restores NK-cell immunosurveillance on CTCs. Competition assays, cytotoxicity experiments with receptor-specific antibodies, FAK/JNK/c-Jun pathway western blotting, in vivo metastasis models Hepatology (Baltimore, Md.) High 38779918
2022 TIGIT expression on B cells suppresses proliferation of IL-17-producing circulating follicular helper T cells (cTfh) via the TIGIT/CD155 axis; impaired TIGIT expression on MS-derived B cells (mediated by dysregulation of TCF4) leads to expansion of activated cTfh cells in multiple sclerosis. Co-culture of TIGIT+ B cells with CD155-expressing cTfh cells, TIGIT/CD155 axis blockade, TCF4 transcription factor analysis, flow cytometry The Journal of clinical investigation Medium 36250467
2023 TIGIT-KO mice are significantly protected from ischemic and nephrotoxic AKI; TIGIT-expressing kidney T cells have effector/central memory phenotype and proinflammatory profile; scRNA-seq analysis shows enrichment of oxidative phosphorylation and mTORC1 signaling genes in Th17 cells from TIGIT-KO mice. TIGIT knockout mice in ischemia reperfusion and cisplatin AKI models, RNA-Seq, flow cytometry, scRNA-seq Journal of the American Society of Nephrology : JASN Medium 36747315
2022 CD226 signals promote the early phase of human Tfh cell differentiation by driving proliferation of naive CD4+ T cells and Tfh precursors, while TIGIT (highly expressed on germinal center Tfh cells) attenuates CD226 signals post-GC Tfh maturation; blocking CD226 inhibits proliferation and Tfh marker expression at early stages but increases CXCR5, ICOS, and IL-21 in mature GC-Tfh. Artificial APC culture system with CD155, CD226 blocking antibody, flow cytometry for Tfh markers, cytokine measurement Frontiers in immunology Medium 35273617
2020 TIGIT modulation alters the phenotype and cytokine profile of T cells during influenza and chronic LCMV infection and induces IL-10 expression, limiting immune pathology in peripheral organs; however, TIGIT does not affect virus control in vivo. TIGIT modulation in influenza and chronic LCMV mouse models, cytokine profiling, organ pathology assessment Nature communications High 32152316
2018 MEG3 (lncRNA) modulates TIGIT expression in CD4+ T cells by sponging miR-23a; MEG3 overexpression sequesters miR-23a, increasing TIGIT expression, which in turn suppresses Th1/Th17 differentiation and reduces IFN-γ and TNF-α in a mouse model of aplastic anemia. MEG3 overexpression, miR-23a sponging assay, TIGIT expression measurement, mouse aplastic anemia model Molecular and cellular biochemistry Medium 30382432

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity 1722 27192565
2015 Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 1148 25680274
2014 The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer cell 982 25465800
2018 Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nature immunology 891 29915296
2020 TIGIT in cancer immunotherapy. Journal for immunotherapy of cancer 635 32900861
2019 TIGIT as an emerging immune checkpoint. Clinical and experimental immunology 436 31828774
2017 TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunological reviews 378 28258695
2023 Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy. Journal of hematology & oncology 302 37670328
2011 Vstm3 is a member of the CD28 family and an important modulator of T-cell function. European journal of immunology 280 21416464
2024 LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity 201 38354701
2016 Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 192 27620276
2021 TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer. Frontiers in immunology 184 34367161
2022 TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy. Journal for immunotherapy of cancer 180 35379739
2023 Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials. Molecular cancer 178 37291608
2019 DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers 175 31234588
2018 TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer immunology, immunotherapy : CII 158 30232519
2017 Tim-3, Lag-3, and TIGIT. Current topics in microbiology and immunology 126 28900677
2017 Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions. Cancer immunology, immunotherapy : CII 125 28623459
2023 Anti-TIGIT therapies for solid tumors: a systematic review. ESMO open 124 36933320
2021 TIGIT/CD226 Axis Regulates Anti-Tumor Immunity. Pharmaceuticals (Basel, Switzerland) 103 33670993
2019 TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma. Cancer immunology research 87 30659053
2024 Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy. Cancer cell 78 38181797
2024 Targeting TIGIT for cancer immunotherapy: recent advances and future directions. Biomarker research 78 38229100
2021 PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells. Molecular therapy : the journal of the American Society of Gene Therapy 75 34628052
2023 TIGIT, a novel immune checkpoint therapy for melanoma. Cell death & disease 73 37495610
2022 Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer. Journal of translational medicine 73 35729552
2022 TIGIT blockade repolarizes AML-associated TIGIT+ M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis. Journal for immunotherapy of cancer 72 36549780
2022 TIGIT is the central player in T-cell suppression associated with CAR T-cell relapse in mantle cell lymphoma. Molecular cancer 67 36163179
2020 TIGIT limits immune pathology during viral infections. Nature communications 67 32152316
2019 Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer. Disease markers 63 30733837
2019 A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function. Journal for immunotherapy of cancer 63 31500665
2024 Platelet-mediated circulating tumor cell evasion from natural killer cell killing through immune checkpoint CD155-TIGIT. Hepatology (Baltimore, Md.) 61 38779918
2021 Targeting TIGIT for Immunotherapy of Cancer: Update on Clinical Development. Biomedicines 61 34572463
2024 Promising immunotherapy targets: TIM3, LAG3, and TIGIT joined the party. Molecular therapy. Oncology 59 38596295
2020 Targeting the "PVR-TIGIT axis" with immune checkpoint therapies. F1000Research 58 32489646
2021 CD155/TIGIT, a novel immune checkpoint in human cancers (Review). Oncology reports 57 33469677
2023 Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial. JAMA oncology 56 37768658
2017 TIGIT signalling pathway negatively regulates CD4+ T-cell responses in systemic lupus erythematosus. Immunology 55 28108989
2019 Expression of TIGIT/CD155 and correlations with clinical pathological features in human hepatocellular carcinoma. Molecular medicine reports 53 31485637
2022 Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer. Cancer immunology, immunotherapy : CII 52 35292828
2021 DNAM-1 versus TIGIT: competitive roles in tumor immunity and inflammatory responses. International immunology 49 34694361
2021 Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML. International journal of molecular sciences 48 34884723
2023 TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation. Nature communications 46 37596248
2021 Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy. BMB reports 44 33298247
2017 Contribution of inhibitory receptor TIGIT to NK cell education. Journal of autoimmunity 44 28438433
2022 Update in TIGIT Immune-Checkpoint Role in Cancer. Frontiers in oncology 43 35656508
2022 TIGIT as a Promising Therapeutic Target in Autoimmune Diseases. Frontiers in immunology 42 35720417
2020 The relationship between TIGIT+ regulatory T cells and autoimmune disease. International immunopharmacology 40 32172208
2020 Immune checkpoint targeting TIGIT in hepatocellular carcinoma. American journal of translational research 40 32774695
2016 TIGIT, A Novel Therapeutic Target for Tumor Immunotherapy. Immunological investigations 40 27819527
2022 Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer. Cells 39 35326415
2022 Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis. The Journal of clinical investigation 36 36250467
2021 PET Imaging of TIGIT Expression on Tumor-Infiltrating Lymphocytes. Clinical cancer research : an official journal of the American Association for Cancer Research 34 33408249
2018 Expression of the immune checkpoint receptor TIGIT in Hodgkin's lymphoma. BMC cancer 34 30514251
2020 Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology(R) neuroimmunology & neuroinflammation 31 32269065
2024 Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response. Cell reports. Medicine 30 39591972
2022 TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation Against Cancer. Frontiers in immunology 30 35320940
2019 Treatment of murine lupus with TIGIT-Ig. Clinical immunology (Orlando, Fla.) 30 31005675
2020 Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients. BioMed research international 29 32802845
2019 Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome. Leukemia & lymphoma 27 30638415
2022 CD226 and TIGIT Cooperate in the Differentiation and Maturation of Human Tfh Cells. Frontiers in immunology 26 35273617
2022 Role of CD155/TIGIT in Digestive Cancers: Promising Cancer Target for Immunotherapy. Frontiers in oncology 26 35433470
2020 Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency. Immunological investigations 26 32397769
2023 TIGIT signaling and its influence on T cell metabolism and immune cell function in the tumor microenvironment. Frontiers in oncology 25 36874131
2018 MEG3 modulates TIGIT expression and CD4 + T cell activation through absorbing miR-23a. Molecular and cellular biochemistry 25 30382432
2025 TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies. Cell death & disease 24 40890162
2023 Tiragolumab (Anti-TIGIT) in SCLC: Skyscraper-02, a Towering Inferno. Lung Cancer (Auckland, N.Z.) 24 36636263
2023 Immune Checkpoint Molecule TIGIT Regulates Kidney T Cell Functions and Contributes to AKI. Journal of the American Society of Nephrology : JASN 24 36747315
2023 GITR and TIGIT immunotherapy provokes divergent multicellular responses in the tumor microenvironment of gastrointestinal cancers. Genome medicine 24 38008725
2022 Clinical Development of Anti-TIGIT Antibodies for Immunotherapy of Cancer. Current oncology reports 24 35412226
2022 TIGIT: A promising target to overcome the barrier of immunotherapy in hematological malignancies. Frontiers in oncology 24 36605439
2023 TIGIT: An emerging immune checkpoint target for immunotherapy in autoimmune disease and cancer. International immunopharmacology 23 37262959
2022 The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients. Cancers 23 36497240
2024 TGF-β-mediated crosstalk between TIGIT+ Tregs and CD226+CD8+ T cells in the progression and remission of type 1 diabetes. Nature communications 21 39406740
2021 TIGIT and CD155 as Immune-Modulator Receptor and Ligand on CD4+ T cells in Preeclampsia Patients. Immunological investigations 20 33855917
2020 TIGIT Blockade: A Multipronged Approach to Target the HIV Reservoir. Frontiers in cellular and infection microbiology 20 32432050
2022 PVR/TIGIT and PD-L1/PD-1 expression predicts survival and enlightens combined immunotherapy in lung squamous cell carcinoma. Translational oncology 19 35926369
2024 Clinical response and pathway-specific correlates following TIGIT-LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial. Nature cancer 18 39187595
2023 Molecular and structural basis of TIGIT: Nectin-4 interaction, a recently discovered pathway crucial for cancer immunotherapy. Biochemical and biophysical research communications 18 37542773
2022 TIGIT axis: novel immune checkpoints in anti-leukemia immunity. Clinical and experimental medicine 18 35419661
2021 Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity. The Journal of infectious diseases 18 33744939
2023 TIGIT inhibition and lenalidomide synergistically promote antimyeloma immune responses after stem cell transplantation in mice. The Journal of clinical investigation 17 36512425
2023 TIGIT mediates activation-induced cell death of ILC2s during chronic airway allergy. The Journal of experimental medicine 17 37036426
2023 Studying TIGIT activity against tumors through the generation of knockout mice. Oncoimmunology 17 37261087
2022 Gene of the month: T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). Journal of clinical pathology 17 35058314
2022 Structural and functional characterization of a monoclonal antibody blocking TIGIT. mAbs 17 35090381
2020 TIM-3 and TIGIT are possible immune checkpoint targets in patients with bladder cancer. Urologic oncology 17 32665122
2023 The co-inhibitory receptor TIGIT regulates NK cell function and is upregulated in human intrahepatic CD56bright NK cells. Frontiers in immunology 16 36845105
2022 TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer. British journal of cancer 16 35039625
2022 Co-Expression of TIGIT and Helios Marks Immunosenescent CD8+ T Cells During Aging. Frontiers in immunology 16 35651622
2023 TIGIT is a key inhibitory checkpoint receptor in lymphoma. Journal for immunotherapy of cancer 15 37364933
2025 Tiragolumab and TIGIT: pioneering the next era of cancer immunotherapy. Frontiers in pharmacology 14 40567374
2024 Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis. Frontiers in immunology 13 38745667
2022 TIGIT Signaling Pathway Regulates Natural Killer Cell Function in Chronic Hepatitis B Virus Infection. Frontiers in medicine 13 35265633
2019 Expression of the immune checkpoint receptor TIGIT in seminoma. Oncology letters 13 31423216
2025 TIGIT deficiency promotes autoreactive CD4+ T-cell responses through a metabolic‒epigenetic mechanism in autoimmune myositis. Nature communications 12 40374622
2023 Self-delivery of TIGIT-blocking scFv enhances CAR-T immunotherapy in solid tumors. Frontiers in immunology 12 37359558
2022 Increased expression of TIGIT and KLRG1 correlates with impaired CD56bright NK cell immunity in HPV16-related cervical intraepithelial neoplasia. Virology journal 12 35413989
2024 CD155-TIGIT Axis as a Therapeutic Target for Cancer Immunotherapy. Current medicinal chemistry 11 38666504
2023 Peptide-based PET imaging agent of tumor TIGIT expression. EJNMMI research 11 37129788

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