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GENE:

TNFRSF4 (TNF Receptor Superfamily Member 4)

i
Other names: TNFRSF4, TNF Receptor Superfamily Member 4 , TAX Transcriptionally-Activated Glycoprotein 1 Receptor, Tumor Necrosis Factor Receptor Superfamily Member 4, OX40L Receptor, ACT35 Antigen, CD134 Antigen, TXGP1L, Tax-Transcriptionally Activated Glycoprotein 1 Receptor, Tumor Necrosis Factor Receptor Superfamily, Member 4, Lymphoid Activation Antigene ACT35, OX40 Cell Surface Antigen, OX40 Homologue, ATC35 Antigen, OX40 Antigen, ACT35, CD134, IMD16, OX40
9d
Y chromosome-linked EIF1AY deletion drives sex differences in multiple myeloma. (PubMed, NPJ Precis Oncol)
These findings uncover a feed-forward loop in which the RPS4Y1-EIF1AY-CD134 axis suppresses IL-4/IL-13-DDR1 signaling, thereby suppressing M2 macrophage polarization and recruitment, and sustaining tumor growth through reciprocal crosstalk between tumor cells and macrophages. Collectively, our study elucidates a novel immune regulatory pathway driving sex differences in MM and highlights EIF1AY as a promising target for precision immunotherapy in male patients.
Journal • IO biomarker
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TNFRSF4 (TNF Receptor Superfamily Member 4) • IL13 (Interleukin 13) • IL4 (Interleukin 4)
14d
Prognostic immunological implications of OX40L expression in the tumor microenvironment of melanoma. (PubMed, Front Immunol)
OX40L protein expression is a heterogeneous but prominent feature of the melanoma microenvironment, with cell type-specific expression patterns that include regulatory T cells. An exploratory association was seen between myeloid OX40L expression and clinical outcome, warranting further investigation.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • TNFRSF4 (TNF Receptor Superfamily Member 4) • TNFSF4 (TNF Superfamily Member 4)
19d
Current status and perspective of immunotherapy for head and neck squamous cell carcinoma. (PubMed, Expert Opin Investig Drugs)
Currently, pembrolizumab plus or less chemotherapy is recommended in patients with CPS > 1 in metastatic HNSCC, while nivolumab is used in the second line setting for platinum-refractory disease. This review discusses both completed and ongoing clinical trials with PD-1/PDL-1 and new checkpoint inhibitors and immunotherapies. It also addresses mechanisms of resistance to immunotherapy, potential therapeutic strategies to overcome this resistance, biomarkers and side effects.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • TNFRSF4 (TNF Receptor Superfamily Member 4)
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Keytruda (pembrolizumab) • Opdivo (nivolumab)
22d
SOX4 drives the differentiation of CD4+T cells toward an immunosuppressive phenotype (PubMed, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi)
Moreover, SOX4 overexpression enhanced ATP production and the levels of mitochondrial respiratory chain complexs while reducing ROS and mtROS levels in CD4+T cells, with no significant change in mitochondrial mass. Conclusion We demonstrate that SOX4 induces a plastic Treg-like state in CD4+T cells, modulates the expression of key molecules associated with Treg suppressive function, and enhances their oxidative phosphorylation.
Journal • PD(L)-1 Biomarker • IO biomarker
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IFNG (Interferon, gamma) • SMAD4 (SMAD family member 4) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1) • TNFRSF4 (TNF Receptor Superfamily Member 4) • FOXP3 (Forkhead Box P3) • IL17A (Interleukin 17A) • YBX1 (Y-Box Binding Protein 1) • IL4 (Interleukin 4) • SMAD2 (SMAD Family Member 2) • SMAD3 (SMAD Family Member 3) • SOX4 (SRY-Box Transcription Factor 4) • TCF4 (Transcription Factor 4)
2ms
Vessels encapsulating tumor clusters promote non-invasive metastasis of hepatocellular carcinoma by shaping an immunosuppressive microenvironment. (PubMed, J Clin Invest)
Collectively, VETC may enhance Tregs' activity via TGF-β1, while Tregs promote and sustain CD8+ T cell exhaustion through immune inhibitory ligand-receptor interaction, thereby shaping immunosuppressive microenvironment and enabling tumor cluster to carry such niche to disseminate. These findings disclose mechanisms of tumor immune microenvironment formation and provide rationales for precision medicine.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • TGFB1 (Transforming Growth Factor Beta 1) • TNFRSF4 (TNF Receptor Superfamily Member 4)
2ms
Immune Checkpoint Remodeling Across Disease Progression in Multiple Myeloma. (PubMed, Neoplasma)
Checkpoint alterations, such as low TIGIT or CTLA-4 and elevated OX40 expression, were correlated with superior progression-free survival. MM progression entails extensive, stage- and subset-specific remodeling of inhibitory and activating immune checkpoints in the BM, with implications for immunotherapeutic targeting.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • ICOS (Inducible T Cell Costimulator) • CD27 (CD27 Molecule) • TNFRSF4 (TNF Receptor Superfamily Member 4) • BTLA (B And T Lymphocyte Associated)
3ms
Association Between FOXP3 and OX40 Expression in Adult T-Cell Leukemia Cells. (PubMed, Viruses)
Furthermore, small interfering RNA-mediated FOXP3 knockdown in HTLV-1-infected cell lines increased OX40L expression. These results suggest that interactions between FOXP3- OX40L+ cells and FOXP3+ OX40+ cells may promote the proliferation of FOXP3+ ATL cells.
Journal • IO biomarker
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TNFRSF4 (TNF Receptor Superfamily Member 4) • FOXP3 (Forkhead Box P3) • TNFSF4 (TNF Superfamily Member 4)
3ms
The oncogenic role of BCL2L12 associated with immune status in the prognosis of human hepatocellular carcinoma. (PubMed, Naturwissenschaften)
Panobinostat, Pirinixic acid, and Fluorouracil were predicted to be the potential BCL2L12-targeted drug for HCC. Our findings offer an understanding of the Oncogenic Role of BCL2L12 associated with immune status in the prognosis of HCC and provide potential strategies for currently limited treatment.
Journal • IO biomarker
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TNFRSF4 (TNF Receptor Superfamily Member 4) • BCL2L12 (BCL2 Like 12) • MIR4435-2HG (MIR4435-2 Host Gene) • CYTOR (Cytoskeleton Regulator RNA)
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5-fluorouracil • Farydak (panobinostat)
3ms
Enhanced anti-tumor efficacy of tumor-infiltrating lymphocytes by GITR agonist in ovarian cancer. (PubMed, Front Immunol)
Taken together, we demonstrated that the addition of an agonistic GITR antibody during the early phase of TIL culture increased the CD8+ T cell to Treg cell ratio and enhanced anti-tumor T cell immunity. Enhancing TILs with a GITR agonist may be beneficial for improving the clinical outcomes of TIL-based ACT in OC.
Journal • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • BCL2L1 (BCL2-like 1) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • CSF2 (Colony stimulating factor 2) • GZMB (Granzyme B) • TNFRSF4 (TNF Receptor Superfamily Member 4) • IL15 (Interleukin 15) • IL21 (Interleukin 21)
3ms
OX-40 signaling promotes tumorigenesis in CTCL by regulating ERK activation. (PubMed, Front Immunol)
Therefore, the in vivo chick embryo metastasis model may serve as a valuable preclinical tool for identifying novel anti-tumor targets in CTCL. The OX-40 axis was identified as a key driver of CTCL progression, promoting tumor growth and metastasis through ERK activation while validating the chick embryo model as a preclinical tool for therapeutic testing.
Journal • IO biomarker
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VEGFC (Vascular Endothelial Growth Factor C) • TNFRSF4 (TNF Receptor Superfamily Member 4) • TNFSF4 (TNF Superfamily Member 4)
3ms
Microwave ablation triggers OX40L-mediated disruption of TNFRSF4+ Treg immunosuppressive activity. (PubMed, Front Immunol)
Mechanistically, MWA suppressed NF-κB/IκBα/TRAF6 signaling, and these effects were amplified by an OX40 agonist, suggesting the pathway is potentially OX40L-dependent. This study demonstrates that MWA disrupts Treg immunosuppression, likely by activating OX40L/TNFRSF4 signaling, and favorably alters the balance of effector to suppressor cells, providing a novel rationale for combining thermal ablation with OX40-targeted immunotherapies in cancer treatment.
Journal
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CD8 (cluster of differentiation 8) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TNFRSF4 (TNF Receptor Superfamily Member 4) • NFKBIA (NFKB Inhibitor Alpha 2) • TNFSF4 (TNF Superfamily Member 4) • TRAF6 (TNF Receptor Associated Factor 6)
3ms
Single-cell analysis of tumor microenvironment immune homeostasis and identification of prognostic biomarkers in head and neck squamous cell carcinoma. (PubMed, Transl Cancer Res)
This study provides valuable insights into the immune dynamics of HNSCC and identifies a prognostic risk model based on key immune-related genes, aiding in personalized treatment strategies. The findings offer a novel approach for precise prognostic evaluation and targeted therapy development in HNSCC, advancing clinical management and patient outcomes.
Journal • IO biomarker
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SERPINH1 (Serpin family H member 1) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • TNFRSF4 (TNF Receptor Superfamily Member 4) • FOXP3 (Forkhead Box P3) • STAG3 (Stromal Antigen 3) • NKG7 (Natural Killer Cell Granule Protein 7) • PLAU (Plasminogen Activator)