ArticleThe Journal of clinical investigation2018
An osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
252 citing papers in PubMed, 1 synthesis or guideline pooled it, 362 citations in OpenAlex.
- The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.Frontiers in immunology · 2023Pooled it
- Trial
- A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer.JNCI cancer spectrum · 2024Trial
- Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.Cancer biology & therapy · 2026Review
- The tumoural landscape of lymphocytes and immune pathways in immunotherapy-treated melanoma patients.Genes and immunity · 2026Article
- Extracellular matrix remodeling and immune reprogramming drive residual tumor progression of liver cancer after incomplete microwave ablation.Molecular oncology · 2026Article
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Macrophage PABPC4-SPP1 Axis Orchestrates Immunosuppression in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Environmentally induced cell stiffening shapes metastatic site selection by tuning the immune vulnerability of cancer cells.Immunity · 2026Article
- A mechanosensitive gene signature associated with immune landscape and survival in glioma: a multi-cohort analysis.Neurological research and practice · 2026Article
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- SPP1-positive macrophages drive trastuzumab resistance in HER2-positive breast cancer.Cell communication and signaling : CCS · 2026Article
- Osteopontin mediates acquired resistance to hypoxia-inducing antiangiogenics and promotes anti-PD-L1 refractoriness in breast cancer models.The Journal of clinical investigation · 2026Article
- Exploratory Analysis of Autophagy-related Genes and Immune Infiltration in Human Hippocampal Tissue of Temporal Lobe Epilepsy.Molecular neurobiology · 2026Article
- Preliminary study on the mechanism of OPN up-regulating PD-L1 to induce CD8 + T cell exhaustion in synovial sarcoma.BMC cancer · 2026Article
- A Multicellular Coordinated Network Driving Lymphovascular Space Invasion in Endometrioid Endometrial Carcinoma.Cell proliferation · 2026Article
- Single-cell and multi-omics integration delineates the landscape of gene-wise intratumor heterogeneity and identifies prognostic biomarkers for immunotherapy in non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Clinicopathological characteristics of patients with inoperable non-small cell lung cancer harboring circulating NRF2 pathway mutations.The Journal of pathology · 2026Article
- Osteopontin-driven TGF-β1 signaling via integrin αvβ3-NF-κB axis impairs NK cell function in head and neck squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
192 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
Abstract
Despite breakthroughs in immune checkpoint inhibitor (ICI) immunotherapy, not all human cancers respond to ICI immunotherapy and a large fraction of patients with the responsive types of cancers do not respond to current ICI immunotherapy. This clinical conundrum suggests that additional immune checkpoints exist. We report here that interferon regulatory factor 8 (IRF8) deficiency led to impairment of cytotoxic T lymphocyte (CTL) activation and allograft tumor tolerance. However, analysis of chimera mice with competitive reconstitution of WT and IRF8-KO bone marrow cells as well as mice with IRF8 deficiency only in T cells indicated that IRF8 plays no intrinsic role in CTL activation. Instead, IRF8 functioned as a repressor of osteopontin (OPN), the physiological ligand for CD44 on T cells, in CD11b+Ly6CloLy6G+ myeloid cells and OPN acted as a potent T cell suppressor. IRF8 bound to the Spp1 promoter to repress OPN expression in colon epithelial cells, and colon carcinoma exhibited decreased IRF8 and increased OPN expression. The elevated expression of OPN in human colon carcinoma was correlated with decreased patient survival. Our data indicate that myeloid and tumor cell-expressed OPN acts as an immune checkpoint to suppress T cell activation and confer host tumor immune tolerance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.