OX40 (CD134) and OX40 ligand, important immune checkpoints in cancer

Abstract Immunotherapy has shown promising results in cancer treatment. Research shows that most patients might be resistant to these therapies. So, new immune therapies are needed. OX40 (CD134) and OX40 ligand (OX40L), costimulatory molecules, express on different types of immune cells. The interaction between OX40 and OX40L (OX40/OX40L) induces the expansion and proliferation of T cells and decreases the immunosuppression of regulatory T (Treg) cells to enhance the immune response to the specific antigen. For the important role OX40 takes in the process of immunity, many clinical trials are focusing on OX40 to find out whether it may have active effects in clinical cancer treatment. The results of clinical trials are still not enough. So, we reviewed the OX40 and its ligand (OX40L) function in cancer, clinical trials with OX40/OX40L and the correlation between OX40/OX40L and other immune checkpoints to add more ideas to tumor feasible treatment.

• Publication year

  2019

• Venue

  OncoTargets and Therapy

• Publication date

  2019-09-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2147/OTT.S214211PMID 31564917PMCID 6735535
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Central Roles of OX40L–OX40 Interaction in the Induction and Progression of Human T Cell–Driven Acute Graft-versus-Host Disease

  2019cited by this paper
• OX40 stimulation and PD-L1 blockade synergistically augment HBV-specific CD4 T cells in patients with HBeAg-negative infection.

  2019cited by this paper
• Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity.

  2019cited by this paper
• The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy.

  2018cited by this paper
• PD-1 and cancer: molecular mechanisms and polymorphisms

  2018cited by this paper
• Targeting Costimulatory Pathways in Systemic Sclerosis

  2018cited by this paper
• Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy

  2018cited by this paper
• Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking

  2018cited by this paper
• Agonist OX40 immunotherapy improves survival in glioma-bearing mice and is complementary with vaccination with irradiated GM-CSF–expressing tumor cells

  2018cited by this paper
• Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients

  2018cited by this paper
• The Immune Checkpoint Modulator OX40 and Its Ligand OX40L in NK-Cell Immunosurveillance and Acute Myeloid Leukemia

  2018cited by this paper
• PD-1/PD-L1 in disease.

  2018cited by this paper
• Could OX40 agonist antibody promote activation of the anti‐tumor immune response in gastric cancer?

  2018cited by this paper
• Anti-CD73 and anti-OX40 immunotherapy coupled with a novel biocompatible enzyme prodrug system for the treatment of recurrent, metastatic ovarian cancer.

  2018cited by this paper
• Antigen-Specific Antitumor Responses Induced by OX40 Agonist Are Enhanced by the IDO Inhibitor Indoximod

  2018cited by this paper
• In vivo antitumor function of tumor antigen‐specific CTLs generated in the presence of OX40 co‐stimulation in vitro

  2018cited by this paper
• Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis

  2018cited by this paper
• 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

  2018cited by this paper
• Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies.

  2018cited by this paper
• A STING Agonist Given with OX40 Receptor and PD-L1 Modulators Primes Immunity and Reduces Tumor Growth in Tolerized Mice

  2017cited by this paper
• MHC class II expression in lung cancer.

  2017cited by this paper
• Immunotherapy of Prostate Cancer: Facts and Hopes

  2017cited by this paper
• Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis.

  2017cited by this paper
• 4-1BB Agonist Focuses CD8+ Tumor-Infiltrating T-Cell Growth into a Distinct Repertoire Capable of Tumor Recognition in Pancreatic Cancer

  2017cited by this paper
• Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis

  2017cited by this paper
• PD-1, PD-L1 Protein Expression in Non-Small Cell Lung Cancer and Their Relationship with Tumor-Infiltrating Lymphocytes

  2017cited by this paper
• Local checkpoint inhibition of CTLA‐4 as a monotherapy or in combination with anti‐PD1 prevents the growth of murine bladder cancer

  2017cited by this paper
• CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes.

  2017cited by this paper
• LAG‐3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD‐1/PD‐L1 and Tumor‐Infiltrating Lymphocytes

  2017cited by this paper
• Role of PD-1 in Immunity and Diseases.

  2017cited by this paper
• Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer

  2017cited by this paper
• OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal Center Reactions during Infection

  2017cited by this paper
• OX40 signaling is involved in the autoactivation of CD4+CD28− T cells and contributes to the pathogenesis of autoimmune arthritis

  2017cited by this paper
• CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function

  2017cited by this paper
• Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40

  2017cited by this paper
• CTLA-4, an Essential Immune-Checkpoint for T-Cell Activation.

  2017cited by this paper
• Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling

  2017cited by this paper
• Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade.

  2017cited by this paper
• Mast Cell-Derived Exosomes Promote Th2 Cell Differentiation via OX40L-OX40 Ligation

  2016cited by this paper
• Lymphocyte‐activation gene‐3, an important immune checkpoint in cancer

  2016cited by this paper
• Surface expression of inhibitory (CTLA-4) and stimulatory (OX40) receptors by CD4+ regulatory T cell subsets circulating in human malaria.

  2016cited by this paper
• OX40L blockade protects against inflammation-driven fibrosis

  2016cited by this paper
• Rationale for anti-OX40 cancer immunotherapy.

  2016cited by this paper
• OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential

  2016cited by this paper
• 4-1BB agonism: adding the accelerator to cancer immunotherapy

  2016cited by this paper
• OX40, PD-1 and CTLA-4 are selectively expressed on tumor-infiltrating T cells in head and neck cancer

  2016cited by this paper
• Enhancement of CD4(+) T cell response and survival via coexpressed OX40/OX40L in Graves' disease.

  2016cited by this paper
• Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice

  2016cited by this paper
• Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets.

  2016cited by this paper
• OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment.

  2016cited by this paper
• Agonists of Co-stimulation in Cancer Immunotherapy Directed Against CD137, OX40, GITR, CD27, CD28, and ICOS.

  2015cited by this paper
• 4-1BB Signaling Enhances Primary and Secondary Population Expansion of CD8+ T Cells by Maximizing Autocrine IL-2/IL-2 Receptor Signaling

  2015cited by this paper
• OX40- and CD27-Mediated Costimulation Synergizes with Anti–PD-L1 Blockade by Forcing Exhausted CD8+ T Cells To Exit Quiescence

  2015cited by this paper
• 4-1BB Agonists: Multi-Potent Potentiators of Tumor Immunity

  2015cited by this paper
• OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

  2015cited by this paper
• Combined OX40 ligation plus CTLA-4 blockade

  2014cited by this paper
• PD-1 Blockade and OX40 Triggering Synergistically Protects against Tumor Growth in a Murine Model of Ovarian Cancer

  2014cited by this paper
• Blockade of the OX40/OX40L pathway and induction of PD-L1 synergistically protects mouse islet allografts from rejection.

  2014cited by this paper
• Exogenous OX40 Stimulation during Lymphocytic Choriomeningitis Virus Infection Impairs Follicular Th Cell Differentiation and Diverts CD4 T Cells into the Effector Lineage by Upregulating Blimp-1

  2013cited by this paper
• Concomitant Increase of OX40 and FOXP3 transcripts in peripheral blood of patients with breast cancer.

  2013cited by this paper
• OX40 is a potent immune-stimulating target in late-stage cancer patients.

  2013cited by this paper
• The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy.

  2013cited by this paper
• Anti-CTLA-4 Antibodies of IgG2a Isotype Enhance Antitumor Activity through Reduction of Intratumoral Regulatory T Cells

  2013cited by this paper
• A Diametric Role for OX40 in the Response of Effector/Memory CD4+ T Cells and Regulatory T Cells to Alloantigen

  2013cited by this paper
• Combined Targeting of Costimulatory (OX40) and Coinhibitory (CTLA-4) Pathways Elicits Potent Effector T Cells Capable of Driving Robust Antitumor Immunity

  2013cited by this paper
• OX40-OX40L expression in idiopathic inflammatory myopathies.

  2013cited by this paper
• Breakthrough of the year 2013. Cancer immunotherapy.

  2013cited by this paper
• OX40 Facilitates Control of a Persistent Virus Infection

  2012cited by this paper
• Activation of OX40 prolongs and exacerbates autoimmune experimental uveitis.

  2011cited by this paper
• OX40 is required for regulatory T cell–mediated control of colitis

  2010cited by this paper
• Anti-OX40 Prevents Effector T-Cell Accumulation and CD8+ T-Cell Mediated Skin Allograft Rejection

  2010cited by this paper
• A non‐redundant role for OX40 in the competitive fitness of Treg in response to IL‐2

  2010cited by this paper
• OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor.

  2008cited by this paper
• OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice.

  2007cited by this paper
• OX40-OX40 Ligand Interaction through T Cell-T Cell Contact Contributes to CD4 T Cell Longevity1

  2006cited by this paper
• Functional Dichotomy between OX40 and 4-1BB in Modulating Effector CD8 T Cell Responses1

  2006cited by this paper
• Critical, but Conditional, Role of OX40 in Memory T Cell-Mediated Rejection1

  2006cited by this paper
• OX40 and Bcl-xL Promote the Persistence of CD8 T Cells to Recall Tumor-Associated Antigen1

  2005cited by this paper
• Immunotherapeutic potential of DISC-HSV and OX40L in cancer

  2005cited by this paper
• During Viral Infection of the Respiratory Tract, CD27, 4-1BB, and OX40 Collectively Determine Formation of CD8+ Memory T Cells and Their Capacity for Secondary Expansion1

  2005cited by this paper
• This information is current as Responses Facilitate Robust CD 8 and CD 4 Recall 4-1 BB and OX 40 Act Independently to and

  2004cited by this paper
• 4-1BB and OX40 Dual Costimulation Synergistically Stimulate Primary Specific CD8 T Cells for Robust Effector Function1

  2004cited by this paper
• Breakthrough of the Year

  2004cited by this paper
• 4‐1BB and OX40 stimulation enhance CD8 and CD4 T‐cell responses to a DNA prime, poxvirus boost vaccine

  2004cited by this paper
• Adenovirus vector-mediated in vivo gene transfer of OX40 ligand to tumor cells enhances antitumor immunity of tumor-bearing hosts.

  2004cited by this paper
• Distinct Roles for the OX40-OX40 Ligand Interaction in Regulatory and Nonregulatory T Cells1

  2004cited by this paper
• OX40 (CD134) Blockade Inhibits the Co-stimulatory Cascade and Promotes Heart Allograft Survival

  2004cited by this paper
• Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

  2004cited by this paper
• Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis.

  2003cited by this paper
• CD134 plays a crucial role in the pathogenesis of EAE and is upregulated in the CNS of patients with multiple sclerosis.

  2003cited by this paper
• Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo

  2003cited by this paper
• Survival in human colorectal cancer correlates with expression of the T-cell costimulatory molecule OX-40 (CD134).

  2002cited by this paper
• 4-1BB Ligand Induces Cell Division, Sustains Survival, and Enhances Effector Function of CD4 and CD8 T Cells with Similar Efficacy1

  2001cited by this paper
• OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells.

  2001cited by this paper
• Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis

  2001cited by this paper
• Induction of Anti-Mammary Cancer Immunity by Engaging the OX-40 Receptor in Vivo

  2001cited by this paper
• Engagement of the OX-40 Receptor In Vivo Enhances Antitumor Immunity1

  2000cited by this paper
• Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor κb Activation, and Bcl-XL Levels in Vivo

  2000cited by this paper
• Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis

  2000cited by this paper
• Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor ␬ B Activation, and Bcl-x L Levels in Vivo

  2000cited by this paper

• Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets

  2026cites this paper
• Tumor microenvironment changes after treatment with avelumab and immune-stimulating agent combinations in patients with advanced solid tumors

  2026cites this paper
• OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.

  2026cites this paper
• Radiopharmaceuticals and their applications in medicine

  2025cites this paper
• Recognition of different subsets of alloreactive T cells by activation-induced markers.

  2025cites this paper
• Brain tumors induce immunoregulatory dendritic cells in draining lymph nodes that can be targeted by OX40 agonist treatment

  2025cites this paper
• Single-cell transcriptomics analysis reveals dynamic changes and prognostic signature in tumor microenvironment of PDAC

  2025cites this paper
• Recent advances in immunotherapy in cancer treatment.

  2024cites this paper
• Unaddressed Challenges in the Treatment of Cutaneous Melanoma?

  2024cites this paper
• Checkpoint Inhibitors in Dogs: Are We There Yet?

  2024cites this paper
• RNA Isoforms as Broad Targets for Cancer Immunotherapy

  2024cites this paper
• An OX-Tra’Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis

  2024cites this paper
• OX40/OX40 ligand and its role in precision immune oncology

  2024cites this paper
• A spatial proteomic study of platinum refractory HGSOC implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment.

  2024cites this paper
• Update on current and new potential immunotherapies in breast cancer, from bench to bedside

  2024cites this paper
• An Engineered Influenza a Virus Expressing the Co-Stimulator OX40L as an Oncolytic Agent Against Hepatocellular Carcinoma

  2024cites this paper
• Beyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity

  2024cites this paper
• SHR-1806, a robust OX40 agonist to promote T cell-mediated antitumor immunity

  2024cites this paper
• Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer

  2024cites this paper
• Preclinical development of a novel CCR8/CTLA-4 bispecific antibody for cancer treatment by disrupting CTLA-4 signaling on CD8 T cells and specifically depleting tumor-resident Tregs

  2024cites this paper
• Deciphering Regulatory T-Cell Dynamics in Cancer Immunotherapy: Mechanisms, Implications, and Therapeutic Innovations.

  2024cites this paper
• Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations

  2024cites this paper
• Barking up the right tree: Immune checkpoint signatures of human and dog cancers

  2024cites this paper
• Immune checkpoint targeting antibodies hold promise for combinatorial cancer therapeutics

  2023cites this paper
• Costimulatory Molecules OX40 and OX40L Upregulation in Oral Squamous Cell Carcinoma: A Blood-Based Study

  2023cites this paper
• Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

  2023cites this paper
• New insight on the correlation of immune landscapes with immune markers expression in different risk classification of gastrointestinal stromal tumors

  2023cites this paper
• Recent Advances in Molecular Mechanisms of Cancer Immunotherapy

  2023cites this paper
• Management of Advanced Invasive Melanoma: New Strategies

  2023cites this paper
• Application and Effectiveness of Chinese Medicine in Regulating Immune Checkpoint Pathways

  2023cites this paper
• Relationship between bladder cancer and polymorphisms of OX40 (rs17568) and OX40L (rs1234313) genes in a Turkish population

  2023cites this paper
• Role of cytokine in malignant T-cell metabolism and subsequent alternation in T-cell tumor microenvironment

  2023cites this paper
• OX40 (CD134) Expression on T Regulatory Cells Is Related to Serious Hypertensive Disorders in Pregnancy

  2023cites this paper
• Dynamic immuno-nanomedicines in oncology.

  2023cites this paper
• Agonistic Bivalent Human scFvs-Fcγ Fusion Antibodies to OX40 Ectodomain Enhance T Cell Activities against Cancer

  2023cites this paper
• Cutaneous leishmaniasis: multiomics approaches to unravel the role of immune cells checkpoints

  2022cites this paper
• The Cellular and Molecular Immunotherapy in Prostate Cancer

  2022influential citation
• Role of TNFSF9 bidirectional signal transduction in antitumor immunotherapy.

  2022cites this paper
• The Treatment of Advanced Melanoma: Therapeutic Update

  2022cites this paper
• Look into my onco-forest - review of plant natural products with anticancer activity.

  2022cites this paper
• PCSK9 Suppresses M2-Like Tumor-Associated Macrophage Polarization by Regulating the Secretion of OX40L from Hepatocellular Carcinoma Cells

  2022cites this paper
• Elevated expression of TNFRSF4 impacts immune cell infiltration and gene mutation in hepatocellular carcinoma

  2022cites this paper
• First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors

  2022cites this paper
• Multifunctional nanomedicines for synergistic photodynamic immunotherapy based on tumor immune microenvironment.

  2022cites this paper
• Ovarian Cancer Immunotherapy en Route: IL9 Inhibits Growth of Ovarian Cancer and Upregulates its Expression of Ox40L and 4-1BBL

  2022cites this paper
• High expression of OX-40, ICOS, and low expression PD-L1 of follicular helper and follicular cytotoxic T cells in chronic lymphocytic leukemia

  2022cites this paper
• In Situ Reprogramming of Tumors for Activating the OX40/OX40 Ligand Checkpoint Pathway and Boosting Antitumor Immunity.

  2022cites this paper
• Serum Levels of OX40 in Early and Late-Stage Oral Squamous Cell Carcinoma

  2021cites this paper
• Immunotherapies targeting stimulatory pathways and beyond

  2021cites this paper
• Next Generation Therapeutic Strateg‐Es: Evolving cancer immunotherapy through agents that Engage, Expand and Enable the anti‐tumor immune response

  2021cites this paper
• Generation and characterization of a high‐affinity chimeric anti‐OX40 antibody with potent antitumor activity

  2021cites this paper
• Turning tumors from cold to inflamed to improve immunotherapy response.

  2021cites this paper
• Expression and Clinical Significance of OX40 and OX40L mRNA in Hepatocellular Carcinoma

  2021cites this paper
• Tackling Immune Targets for Breast Cancer: Beyond PD-1/PD-L1 Axis

  2021cites this paper
• Delivery routes matter: Safety and efficacy of intratumoral immunotherapy.

  2021cites this paper
• Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?

  2021cites this paper
• Tumor-infiltrating CD8+ T cell antitumor efficacy and exhaustion: molecular insights.

  2021cites this paper
• Tilsotolimod: an investigational synthetic toll-like receptor 9 (TLR9) agonist for the treatment of refractory solid tumors and melanoma

  2021influential citation
• Pushing Past the Blockade: Advancements in T Cell-Based Cancer Immunotherapies

  2021cites this paper
• Aging preclinical models in oncology field: from cells to aging

  2021cites this paper
• The landscape of immune checkpoints expression in non-small cell lung cancer: a narrative review

  2021cites this paper
• Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

  2021cites this paper
• B Cells in Atherosclerosis

  2021cites this paper
• TITLE: CIRCULATING IMMUNE BIOMARKERS IN PERIPHERAL BLOOD CORRELATE WITH CLINICAL OUTCOMES IN ADVANCED BREAST CANCER.

  2021cites this paper
• Sono/Photodynamic Nanomedicine‐Elicited Cancer Immunotherapy

  2020cites this paper
• Immunotherapies and Combination Strategies for Immuno-Oncology

  2020cites this paper
• Cancer Immunotherapy Confers a Global Benefit

  2020cites this paper
• Renal Clear Cell Cancer

  2020cites this paper
• The Combination Options and Predictive Biomarkers of PD-1/PD-L1 Inhibitors in Esophageal Cancer

  2020cites this paper
• Development of Genetically Modified Tumor Cell Containing Co-stimulatory Molecule

  2019cites this paper