Affinage

TIGIT

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

Length
244 aa
Mass
26.3 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TIGIT is an inhibitory immune checkpoint receptor expressed on T cells, NK cells, regulatory T cells, ILC2s, and B cells that restrains immune activation through multiple convergent mechanisms: cell-intrinsic signaling via its ITT-like motif that recruits SHIP-1 to suppress NF-κB/ERK pathways, competitive antagonism of the co-activating receptor CD226 for shared nectin-family ligands (CD155/PVR, CD112, nectin-4), and direct disruption of CD226 homodimerization in cis (PMID:21199897, PMID:25465800, PMID:35729552, PMID:37596248). Upon CD155 engagement, TIGIT reorganizes into TCR-proximal nanoclusters at the immune synapse to dampen cytokine secretion, suppresses CD8+ T cell glucose metabolism via inhibition of PI3K/AKT/mTOR signaling, and promotes activation-induced cell death of ILC2s, while on Tregs it enhances suppressive capacity and stability (PMID:37596248, PMID:28883004, PMID:38216949, PMID:37036426, PMID:30046006). TIGIT also functions on B cells to maintain tolerance—B cell-specific TIGIT deletion causes spontaneous CNS inflammation—and its transcriptional regulation involves glucocorticoid receptor signaling and TCF4 (PMID:32668241, PMID:31108170, PMID:36250467). The Fusobacterium nucleatum virulence factor Fap2 directly engages TIGIT to inhibit NK and T cell cytotoxicity, representing a microbial immune evasion strategy, while therapeutic anti-TIGIT antibodies exert effects that depend critically on Fc-FcγR engagement with myeloid cells (PMID:25680274, PMID:33117369, PMID:36512425).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2011 High

    Establishing that TIGIT functions as a T cell-intrinsic co-inhibitory receptor—not merely an APC-targeting molecule—resolved the question of whether TIGIT directly suppresses T cell activation, showing that TIGIT-deficient mice develop hyperproliferative T cell responses and autoimmunity susceptibility.

    Evidence Agonistic anti-TIGIT antibody stimulation, microarray analysis, and TIGIT knockout mouse model

    PMID:21199897

    Open questions at the time
    • Intracellular signaling pathway downstream of TIGIT not yet identified
    • Whether TIGIT inhibition operates on cell types beyond T cells unclear
  2. 2011 High

    Identifying CD155 and CD112 as shared ligands for both TIGIT and the activating receptor CD226 established the TIGIT/CD226 regulatory axis as a paradigm analogous to CTLA-4/CD28, explaining how TIGIT achieves inhibition partly through ligand competition.

    Evidence Ligand binding assays, soluble fusion protein treatment in vitro/in vivo, gene-deficient mouse autoimmune models

    PMID:21416464

    Open questions at the time
    • Whether TIGIT outcompetes CD226 through affinity or stoichiometry not resolved
    • Additional ligands not yet explored
  3. 2014 High

    Demonstrating that TIGIT disrupts CD226 homodimerization in cis and that co-blockade of TIGIT with PD-L1 synergistically restores CD8+ T cell function revealed a dual inhibitory mechanism (ligand competition plus direct receptor-receptor interaction) and established the rationale for combination checkpoint immunotherapy.

    Evidence Antibody blockade in murine tumor and chronic viral infection models, CD226 dimerization assays

    PMID:25465800

    Open questions at the time
    • Structural basis of cis TIGIT-CD226 interaction unresolved
    • Whether cis disruption versus ligand competition dominates in different contexts unknown
  4. 2015 High

    The discovery that Fusobacterium nucleatum Fap2 protein directly binds TIGIT to inhibit NK cell and T cell cytotoxicity revealed a microbial co-option of TIGIT for immune evasion in colorectal cancer.

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

    PMID:25680274

    Open questions at the time
    • Binding interface of Fap2 on TIGIT not structurally characterized
    • Whether other bacterial species exploit TIGIT unknown
  5. 2017 High

    Showing that TIGIT-CD155 interaction drives MHC-I-independent NK cell education and that tumor-derived CD155 suppresses CD8+ T cell glucose metabolism linked TIGIT's inhibitory role to both NK cell maturation and metabolic reprogramming of effector cells.

    Evidence TIGIT-KO and CD155-KO mouse models with NK functional assays; T cell-tumor coculture with CD155 silencing/overexpression and glucose supplementation rescue

    PMID:28438433 PMID:28883004

    Open questions at the time
    • Which metabolic sensors downstream of TIGIT mediate glucose deprivation effects not identified
    • NK education mechanism molecularly undefined
  6. 2018 High

    Demonstrating that TIGIT blockade prevents NK cell exhaustion in tumors and that high TIGIT/low CD226 on tumor-infiltrating Tregs enhances suppressive function established TIGIT as a functional checkpoint on multiple immune cell lineages within the tumor microenvironment.

    Evidence TIGIT antibody blockade in multiple mouse tumor models with NK depletion epistasis; flow cytometry and Treg suppression assays on melanoma patient samples

    PMID:29915296 PMID:30046006

    Open questions at the time
    • Whether TIGIT signaling in Tregs and NK cells uses identical downstream pathways unclear
    • Treg data correlative without genetic Treg-specific deletion
  7. 2019 High

    Identifying glucocorticoid receptor signaling as a direct transcriptional regulator of TIGIT expression on T cells linked neuroendocrine stress pathways to immune checkpoint regulation.

    Evidence GR antagonist RU486 treatment, Lck-Cre conditional GR knockout, corticosterone administration in vitro/in vivo

    PMID:31108170

    Open questions at the time
    • Whether GR binds the TIGIT promoter directly or through intermediary factors not resolved
    • Relevance to tumor-associated stress not tested
  8. 2020 High

    Revealing that membrane-bound CD155 triggers CD226 internalization/degradation on NK cells, that anti-TIGIT therapeutic efficacy requires FcγR engagement on myeloid cells, and that B cell-specific TIGIT deletion causes spontaneous CNS inflammation collectively expanded TIGIT biology beyond direct receptor blockade to include receptor dynamics, Fc-dependent myeloid modulation, and B cell tolerance.

    Evidence CD226 internalization assays and TIGIT-KO NK transfer (PMID:32591463); Fc-functional vs. Fc-null anti-TIGIT antibodies in mouse tumor models (PMID:33117369); B cell-specific conditional TIGIT KO mice developing CNS pathology (PMID:32668241); TIGIT+ B cell co-culture with T cells and DCs (PMID:33750787)

    PMID:32591463 PMID:32668241 PMID:33117369 PMID:33750787

    Open questions at the time
    • Molecular mechanism of Fc-dependent 'reverse activating signals' through FcγR incompletely characterized
    • Whether B cell TIGIT tolerance function is CD155-dependent not definitively shown
  9. 2022 Medium

    Defining the SHIP-1-dependent NF-κB/ERK inhibitory signaling cascade downstream of TIGIT phosphorylation, identifying TCF4 as a transcriptional regulator of TIGIT on B cells, solving the TIGIT–anti-TIGIT antibody crystal structure, and confirming FcγR-dependent anti-TIGIT/lenalidomide synergy in myeloma provided intracellular signaling, transcriptional, structural, and therapeutic mechanistic resolution.

    Evidence Western blot for NF-κB/ERK after TIGIT/CD155 blockade with SHIP-1 recruitment (PMID:35729552); TCF4 dysregulation analysis in MS B cells (PMID:36250467); X-ray crystallography of MG1131-TIGIT complex (PMID:35090381); Fc-functional vs. Fc-null anti-TIGIT with CD8 depletion in myeloma model (PMID:36512425)

    PMID:35090381 PMID:35729552 PMID:36250467 PMID:36512425

    Open questions at the time
    • Whether SHIP-1 is the sole proximal effector or acts with other phosphatases unknown
    • TCF4 regulation based on patient-derived correlative data, direct TCF4 binding to TIGIT locus not shown
  10. 2023 High

    Super-resolution imaging revealed that TIGIT reorganizes into dense nanoclusters at the immune synapse that coalesce with TCR clusters in an ITT-like motif-dependent manner, establishing the spatial mechanism of TIGIT-mediated inhibition; simultaneously, nectin-4 was identified as an additional TIGIT ligand, and TIGIT was shown to mediate ILC2 activation-induced cell death via CD155 on macrophages.

    Evidence Super-resolution microscopy with ITT-motif mutagenesis (PMID:37596248); SPR and structure-guided mutagenesis for nectin-4 binding (PMID:37542773); TIGIT lineage tracer mice, KO, and anti-TIGIT blockade with ILC2 apoptosis assays (PMID:37036426)

    PMID:37036426 PMID:37542773 PMID:37596248

    Open questions at the time
    • Whether nanocluster formation occurs with all TIGIT ligands or is CD155-specific not tested
    • Nectin-4 functional relevance in vivo not established
    • Downstream apoptotic pathway in ILC2s not molecularly defined
  11. 2024 Medium

    Defining PI3K/AKT/mTOR as the metabolic signaling axis suppressed by CD155/TIGIT in CD8+ T cells, and showing that platelet-contact-induced CD155 on circulating tumor cells specifically engages TIGIT (not CD96 or DNAM-1) to evade NK surveillance, refined the metabolic and metastatic evasion mechanisms of the TIGIT axis.

    Evidence Western blotting for PI3K/AKT/mTOR with glucose/lactate assays in TNBC model (PMID:38216949); receptor competition assays and FAK/JNK/c-Jun pathway analysis in hepatocellular CTC-NK model (PMID:38779918)

    PMID:38216949 PMID:38779918

    Open questions at the time
    • Whether PI3K/AKT/mTOR suppression is downstream of SHIP-1 or represents a parallel pathway not resolved
    • In vivo validation of CTC-specific CD155/TIGIT metastasis axis limited to one tumor type

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include: (1) how TIGIT's multiple intracellular signaling modules (ITT-like motif, SHIP-1, PI3K/AKT/mTOR suppression) are hierarchically integrated; (2) whether TIGIT nanocluster formation is ligand-specific and how it relates to cis CD226 disruption at the structural level; (3) the physiological relevance of nectin-4 as a TIGIT ligand in vivo; and (4) which Fc-effector mechanism (ADCC, reverse signaling, or both) drives therapeutic anti-TIGIT antibody efficacy in human tumors.
  • Integrated signaling model connecting SHIP-1, PI3K, and nanocluster formation missing
  • No resolved structure of TIGIT-CD226 cis complex
  • Nectin-4 in vivo studies lacking
  • Human FcγR mechanism for anti-TIGIT not mechanistically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 1
Partners
CD112CD155CD226FAP2NECTIN-4SHIP-1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 TIGIT has T cell-intrinsic inhibitory functions independent of APCs; agonistic anti-TIGIT antibody directly attenuates TCR-driven activation signals in T cells, and TIGIT-deficient mice show hyperproliferative T cell responses and increased susceptibility to autoimmunity. Agonistic anti-TIGIT antibody stimulation, microarray analysis of stimulated T cells, TIGIT knockout mouse model Journal of immunology High 21199897
2011 TIGIT (VSTM3) binds to nectin-family ligands CD155 (PVR) and CD112, which are also ligands for the activating receptor CD226, establishing a regulatory network analogous to CD28/CTLA-4; soluble VSTM3 attenuates T cell responses in vitro and in vivo, and VSTM3-deficient animals are more sensitive to autoimmune challenges. Ligand binding assays, soluble fusion protein treatment in vitro and in vivo, gene-deficient mouse autoimmune models European journal of immunology High 21416464
2014 TIGIT functions as a co-inhibitory receptor that limits CD8+ T cell effector function in tumors and chronic viral infection; CD226 dimerization is disrupted by direct TIGIT–CD226 interaction in cis, and antibody co-blockade of TIGIT and PD-L1 synergistically enhances CD8+ T cell responses. Antibody blockade in murine tumor and viral infection models, assessment of CD226 dimerization upon TIGIT interaction Cancer cell High 25465800
2015 The Fap2 protein of Fusobacterium nucleatum directly interacts with human TIGIT on NK cells and T cells, inhibiting NK cell cytotoxicity and T cell activity, thereby enabling tumor immune evasion. F. nucleatum mutant library screen, direct protein interaction assays, NK cell cytotoxicity assays Immunity High 25680274
2016 TIGIT enhances Th2 recall responses and allergic disease; its interaction with CD155 on dendritic cells promotes Th2 polarization, and in vivo TIGIT blockade suppresses hallmarks of allergic airway disease including lung eosinophilia and IgE production. In vitro Th2 polarization cultures, in vivo allergic airway disease model with TIGIT blockade Journal of immunology Medium 27016609
2017 TIGIT-CD155 interaction promotes NK cell functional maturation (education) in a MHC-I-independent manner; TIGIT+ NK cells from CD155-deficient hosts show functional impairment, and TIGIT deficiency impairs missing-self recognition independently of CD226. TIGIT-KO and CD155-KO mouse models, NK cell functional assays, missing-self rejection assays Journal of autoimmunity High 28438433
2017 CD155/TIGIT signaling inhibits CD8+ T cell metabolism and effector function in gastric cancer; CD155 on gastric cancer cells binds TIGIT and deprives T cells of glucose, impairing IFNγ production, an effect reversed by TIGIT blockade or additional glucose. T cell-tumor coculture assays, CD155 silencing/overexpression, glucose supplementation rescue, in vivo tumor model Cancer research High 28883004
2018 TIGIT is highly expressed on NK cells in tumor-bearing mice and cancer patients; TIGIT blockade prevents NK cell exhaustion and promotes NK cell-dependent tumor immunity and CD8+ T cell tumor-specific immunity. TIGIT antibody blockade in multiple mouse tumor models, NK cell depletion experiments, flow cytometry Nature immunology High 29915296
2018 TIGIT on CD4+ Tregs in melanoma augments Treg suppressive function and stability; high TIGIT expression with low CD226 on Tregs enhances their suppressive capacity, while CD226 expression disrupts Treg suppression. Flow cytometry of patient tumor samples, functional Treg suppression assays, TIGIT/CD226 expression analysis JCI insight Medium 30046006
2019 Glucocorticoid receptor (GR) signaling directly upregulates TIGIT expression on T cells and iNKT cells; stress-induced TIGIT upregulation is reversed by the GR antagonist RU486, and Lck-Cre GR knockout mice fail to upregulate TIGIT under stress. GR antagonist treatment, chemical sympathectomy, Cre/Lox GR conditional knockout, corticosterone administration in vitro and in vivo Brain, behavior, and immunity High 31108170
2020 Membrane-bound CD155 on tumor cells triggers CD226 internalization and degradation on NK cells, resulting in decreased NK cell-mediated tumor reactivity; IL-15 upregulates both TIGIT and CD226 on tumor-infiltrating NK cells and, combined with TIGIT blockade, increases NK cell cytotoxicity. CD226 internalization assays, TIGIT-specific NK cell transfer, mouse melanoma metastasis models, flow cytometry Clinical cancer research High 32591463
2020 TIGIT on memory B cells suppresses immune responses by directly inhibiting T cell proliferation and by arresting pro-inflammatory dendritic cell function via TIGIT/CD155 interactions; TIGIT+ memory B cells also express IL-10, TGF-β1, granzyme B, PD-L1, CD39/CD73, and TIM-1. TIGIT+ B cell isolation, co-culture with T cells and dendritic cells, TIGIT blockade experiments, flow cytometry Nature communications Medium 33750787
2020 B cell-specific TIGIT deletion causes spontaneous CNS inflammation and paralysis; Tim-1 signaling-dependent TIGIT expression on B cells is essential for maintaining CNS-specific tolerance. B cell-specific TIGIT conditional knockout mice, transcriptomic analysis, in vivo neuroinflammation model Cell reports High 32668241
2020 Anti-TIGIT antibody therapeutic effect requires functional Fc binding to FcγRs on myeloid cells; TIGIT blockade does not deplete Tregs but instead induces 'reverse activating signals' through FcγRs causing cytokine/chemokine expression and a granzyme B/perforin response distinct from anti-PD-1. Mouse tumor models with Fc-functional vs. Fc-null anti-TIGIT antibodies, myeloid cell analysis, cytokine profiling Frontiers in immunology Medium 33117369
2022 TIGIT blockade in AML repolarizes TIGIT+ M2 leukemia-associated macrophages to M1 phenotype, increases secretion of M1-associated cytokines, and augments anti-CD47-mediated phagocytosis of AML cells. In vitro TIGIT blockade on primary LAMs, flow cytometry, cytokine measurement, phagocytosis assays Journal for immunotherapy of cancer Medium 36549780
2022 TIGIT, upon binding to CD155, is phosphorylated and recruits SHIP-1, which inhibits NF-κB and ERK activation in CD8+ T cells, resulting in reduced cytokine production; TIGIT blockade attenuates SHIP-1 inhibitory effects and restores NF-κB and ERK signaling. Western blotting for NF-κB and ERK pathway after TIGIT/CD155 blockade, phosphorylation assays, in vivo tumor model Journal of translational medicine Medium 35729552
2022 Impaired TIGIT expression on MS-derived B cells is mediated by dysregulation of transcription factor TCF4; TIGIT on B cells suppresses proliferation of IL-17-producing circulating follicular helper T cells via the TIGIT/CD155 axis. Comparative gene expression analysis, co-culture assays of B cells and cTfh cells, TCF4 dysregulation analysis The Journal of clinical investigation Medium 36250467
2023 TIGIT ligation with CD155 causes TIGIT to reorganize into dense nanoclusters at the immune synapse that coalesce with TCR-rich clusters; this reduces cytokine secretion in a manner dependent on TIGIT's intracellular ITT-like signalling motif, independent of CD226 co-expression. Super-resolution microscopy, immune synapse imaging, ITT-motif mutagenesis, cytokine secretion assays on matched tumor/blood samples Nature communications High 37596248
2023 TIGIT mediates activation-induced cell death (AICD) of ILC2s during chronic airway allergy; ILC2 interaction with CD155 on macrophages promotes apoptosis of TIGIT+ ILC2s, and genetic ablation of Tigit or TIGIT blockade promotes ILC2 survival and worsens chronic allergic inflammation. TIGIT lineage tracer mice, ILC2 apoptosis assays, Tigit knockout mice, anti-TIGIT antagonistic antibody treatment, chromatin accessibility analysis The Journal of experimental medicine High 37036426
2023 TIGIT interacts with nectin-4 as a novel ligand through the membrane-distal ectodomain of nectin-4; this interaction is weaker than TIGIT:nectin-2 binding and inhibits NK cell cytotoxicity; structure-guided mutagenesis mapped the nectin-4 binding interface on TIGIT. Surface plasmon resonance, structure-guided mutagenesis, NK cell cytotoxicity assays Biochemical and biophysical research communications Medium 37542773
2022 Crystal structure of anti-TIGIT antibody MG1131 bound to TIGIT shows that MG1131 blocks the PVR-TIGIT interaction interface; functional assays confirm MG1131 increases NK cell-mediated tumor killing, inhibits Treg suppression, and restores IFNγ secretion from myeloma patient PBMCs. X-ray crystallography, competitive binding assays, NK cytotoxicity assays, Treg suppression assays mAbs High 35090381
2023 Anti-TIGIT agonistic antibody suppresses activation of follicular helper T (Tfh) and peripheral helper T (Tph) cells that highly express TIGIT, and enhances suppressive function of naïve regulatory T cells, in human TIGIT knock-in mice. Anti-hu-TIGIT agonistic mAb generation, hu-TIGIT knock-in mouse model, CD4+ T cell functional assays Communications biology Medium 37161050
2023 Anti-TIGIT activity against myeloma depends on FcγR binding; anti-TIGIT antibodies engaging FcγRs synergize with lenalidomide in a CD8+ T cell-dependent manner post-transplantation, suppressing T cell exhaustion and enhancing effector function specifically in the bone marrow tumor microenvironment. Fc-functional vs. Fc-null anti-TIGIT comparison, CRBN mouse model, CD8+ T cell depletion, bone marrow CD8 T cell phenotyping The Journal of clinical investigation High 36512425
2024 CD155/TIGIT signaling disrupts glucose metabolism of CD8+ T cells in TNBC by suppressing PI3K/AKT/mTOR signaling pathway activation, reducing glycolytic-related proteins and cytokine production; TIGIT blockade restores PI3K/AKT/mTOR activation and cytokine production. Western blotting for PI3K/AKT/mTOR pathway, glucose/lactate assays, in vitro and in vivo TIGIT blockade Cell communication and signaling Medium 38216949
2024 CD155 on CTCs is transcriptionally regulated by the FAK/JNK/c-Jun cascade in a platelet contact-dependent manner; CD155 on CTCs inhibits NK cell cytotoxicity specifically by engaging TIGIT (but not CD96 or DNAM-1), and TIGIT antibody blockade restores NK immunosurveillance and reduces tumor metastasis. Competition assays, cytotoxicity experiments, FAK/JNK/c-Jun pathway analysis, in vitro/ex vivo/in vivo NK assays Hepatology Medium 38779918
2024 TIGIT+CCR7- Tregs inhibit CD226+CCR7-CD8+ cytotoxic T cells via TGF-β signaling in type 1 diabetes; CD226 inhibition in mouse models postpones insulitis onset and reduces hyperglycemia severity. Single-cell RNA sequencing, cell communication analysis, in vitro functional assays, cyclophosphamide- and STZ-induced mouse diabetes models with CD226 inhibition Nature communications Medium 39406740

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 1693 27192565
2015 Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 1123 25680274
2014 The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer cell 968 25465800
2018 Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nature immunology 878 29915296
2020 TIGIT in cancer immunotherapy. Journal for immunotherapy of cancer 621 32900861
2011 Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. Journal of immunology (Baltimore, Md. : 1950) 463 21199897
2017 TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunological reviews 375 28258695
2023 Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy. Journal of hematology & oncology 282 37670328
2017 CD155T/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer. Cancer research 278 28883004
2011 Vstm3 is a member of the CD28 family and an important modulator of T-cell function. European journal of immunology 278 21416464
2018 TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM. Oncoimmunology 274 30221069
2018 TIGIT immune checkpoint blockade restores CD8+ T-cell immunity against multiple myeloma. Blood 245 29986909
2016 Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 191 27620276
2019 DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers 174 31234588
2024 LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity 173 38354701
2023 Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials. Molecular cancer 164 37291608
2018 CD226 opposes TIGIT to disrupt Tregs in melanoma. JCI insight 162 30046006
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
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
2021 TIGIT/CD226 Axis Regulates Anti-Tumor Immunity. Pharmaceuticals (Basel, Switzerland) 100 33670993
2019 TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma. Cancer immunology research 86 30659053
2024 Targeting TIGIT for cancer immunotherapy: recent advances and future directions. Biomarker research 77 38229100
2024 Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy. Cancer cell 75 38181797
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 74 34628052
2022 TIGIT blockade repolarizes AML-associated TIGIT+ M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis. Journal for immunotherapy of cancer 71 36549780
2022 Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer. Journal of translational medicine 69 35729552
2021 Implication of TIGIT+ human memory B cells in immune regulation. Nature communications 67 33750787
2020 PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy. Journal for immunotherapy of cancer 63 33188038
2019 A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function. Journal for immunotherapy of cancer 62 31500665
2019 Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer. Disease markers 61 30733837
2021 Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy. Nature communications 59 34545095
2024 Promising immunotherapy targets: TIM3, LAG3, and TIGIT joined the party. Molecular therapy. Oncology 57 38596295
2020 Targeting the "PVR-TIGIT axis" with immune checkpoint therapies. F1000Research 57 32489646
2020 Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation. Cell reports 56 32668241
2023 Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial. JAMA oncology 54 37768658
2021 TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma. Frontiers in immunology 54 34025646
2017 TIGIT signalling pathway negatively regulates CD4+ T-cell responses in systemic lupus erythematosus. Immunology 54 28108989
2024 Platelet-mediated circulating tumor cell evasion from natural killer cell killing through immune checkpoint CD155-TIGIT. Hepatology (Baltimore, Md.) 52 38779918
2019 Expression of TIGIT/CD155 and correlations with clinical pathological features in human hepatocellular carcinoma. Molecular medicine reports 52 31485637
2022 Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer. Cancer immunology, immunotherapy : CII 50 35292828
2021 DNAM-1 versus TIGIT: competitive roles in tumor immunity and inflammatory responses. International immunology 48 34694361
2023 Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade. Cancer immunology research 47 36689623
2023 TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation. Nature communications 45 37596248
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
2021 Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy. BMB reports 44 33298247
2020 TIGIT enhances CD4+ regulatory T-cell response and mediates immune suppression in a murine ovarian cancer model. Cancer medicine 44 32212317
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
2021 A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment. Scientific reports 41 34795387
2020 Immune checkpoint targeting TIGIT in hepatocellular carcinoma. American journal of translational research 40 32774695
2022 Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer. Cells 38 35326415
2020 The relationship between TIGIT+ regulatory T cells and autoimmune disease. International immunopharmacology 38 32172208
2020 A novel bispecific nanobody with PD-L1/TIGIT dual immune checkpoint blockade. Biochemical and biophysical research communications 38 32782142
2016 TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease. Journal of immunology (Baltimore, Md. : 1950) 38 27016609
2020 Effective Anti-tumor Response by TIGIT Blockade Associated With FcγR Engagement and Myeloid Cell Activation. Frontiers in immunology 37 33117369
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
2021 TIGIT Induces (CD3+) T Cell Dysfunction in Colorectal Cancer by Inhibiting Glucose Metabolism. Frontiers in immunology 33 34659197
2018 Expression of the immune checkpoint receptor TIGIT in Hodgkin's lymphoma. BMC cancer 33 30514251
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
2020 Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency. Immunological investigations 26 32397769
2021 TIGIT blockade enhances NK cell activity against autologous HIV-1-infected CD4+ T cells. Clinical & translational immunology 25 34707863
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 Role of CD155/TIGIT in Digestive Cancers: Promising Cancer Target for Immunotherapy. Frontiers in oncology 24 35433470
2024 Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response. Cell reports. Medicine 23 39591972
2022 Correlation of the TIGIT-PVR immune checkpoint axis with clinicopathological features in triple-negative breast cancer. Frontiers in immunology 23 36544779
2023 Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells. Communications biology 22 37161050
2023 TIGIT: An emerging immune checkpoint target for immunotherapy in autoimmune disease and cancer. International immunopharmacology 22 37262959
2022 The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients. Cancers 22 36497240
2019 Stress-elicited glucocorticoid receptor signaling upregulates TIGIT in innate-like invariant T lymphocytes. Brain, behavior, and immunity 21 31108170
2024 TGF-β-mediated crosstalk between TIGIT+ Tregs and CD226+CD8+ T cells in the progression and remission of type 1 diabetes. Nature communications 19 39406740
2021 A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers. International journal of molecular sciences 19 34638729
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
2021 Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity. The Journal of infectious diseases 18 33744939
2021 A novel scoring system for TIGIT expression in classic Hodgkin lymphoma. Scientific reports 18 33782477
2023 TIGIT inhibition and lenalidomide synergistically promote antimyeloma immune responses after stem cell transplantation in mice. The Journal of clinical investigation 16 36512425
2022 Structural and functional characterization of a monoclonal antibody blocking TIGIT. mAbs 16 35090381
2022 Co-Expression of TIGIT and Helios Marks Immunosenescent CD8+ T Cells During Aging. Frontiers in immunology 16 35651622
2019 Recovery of CD226-TIGIT+FoxP3+ and CD226-TIGIT-FoxP3+ regulatory T cells contributes to clinical remission from active stage in ulcerative colitis patients. Immunology letters 16 31883787
2024 Clinical response and pathway-specific correlates following TIGIT-LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial. Nature cancer 15 39187595
2020 TIM-3 and TIGIT are possible immune checkpoint targets in patients with bladder cancer. Urologic oncology 15 32665122
2023 TIGIT mediates activation-induced cell death of ILC2s during chronic airway allergy. The Journal of experimental medicine 14 37036426
2023 TIGIT is a key inhibitory checkpoint receptor in lymphoma. Journal for immunotherapy of cancer 14 37364933
2023 Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT. Frontiers in immunology 14 37799715
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 Tiragolumab and TIGIT: pioneering the next era of cancer immunotherapy. Frontiers in pharmacology 12 40567374
2024 Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis. Frontiers in immunology 12 38745667
2023 Self-delivery of TIGIT-blocking scFv enhances CAR-T immunotherapy in solid tumors. Frontiers in immunology 12 37359558
2023 Combined Blockade of TIGIT and PD-L1 Enhances Anti-Neuroblastoma Efficacy of GD2-Directed Immunotherapy with Dinutuximab Beta. Cancers 12 37444427
2024 Dual targeting of TIGIT and PD-1 with a novel small molecule for cancer immunotherapy. Biochemical pharmacology 11 38527557
2023 The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy. Haematologica 11 36655432
2023 Peptide-based PET imaging agent of tumor TIGIT expression. EJNMMI research 11 37129788