ArticleCancer research2024
The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses 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
34 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Impact of time-of-day administration of immunotherapy on survival in metastatic renal cell carcinoma: the MOUSEION-09 meta-analysis.Clinical & experimental metastasis · 2024Pooled it
- Role of the circadian rhythm in squamous cell carcinoma: From molecular mechanism to therapy (Review).Molecular medicine reports · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Circadian rhythms and lung cancer biology and immunotherapy: Emerging opportunities and challenges.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Integrative Multi-Omics Analysis Reveals the Immunoregulatory Effects of Sepia Ink on ADHD-like Phenotypes.Current issues in molecular biology · 2026Article
- Dose-resolved control of somatic reprogramming by Rora.Stem cell reports · 2026Article
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment.Acta biochimica et biophysica Sinica · 2026Review
- Glioblastoma stem cells resist cuproptosis with circadian variation of copper levels.The Journal of clinical investigation · 2026Article
- Synchronizing immunity with time: unlocking the potential of chrono-immunotherapy in cancer.Frontiers in immunology · 2026Review
- The gut-skin axis in melanoma: from microbial regulatory mechanisms to clinical translation for precision management.Frontiers in microbiology · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- TCM-Driven Circadian Modulation in Cancer: Engineering Spatiotemporal Drug Delivery for Precision Oncology.International journal of nanomedicine · 2026Review
- RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization.Frontiers in immunology · 2026Review
- Development of a prognostic model for sepsis based on gut microbiota-associated genes and identification of potential targets.Frontiers in medicine · 2026Article
- ChronoimmunoTOX: A Single-Institution Retrospective Study on How the Time of Administration Impacts Immune Checkpoint Inhibitor Efficacy and Toxicity in Melanoma.Journal of clinical medicine · 2025Article
- MCRS1 is associated with immunosuppressive microenvironments in pan-cancer and promotes hepatocellular carcinoma malignant phenotypes.Translational cancer research · 2025Article
- CLOCK-mediated acetylation of NF-κB p65 drives immune evasion in breast cancer.Biology direct · 2025Article
- The prognostic marker NRIP1 is associated with tumor progression and immune infiltration in acute myeloid leukemia.Acta biochimica et biophysica Sinica · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth and shaping the immune microenvironment. Emerging evidence has indicated that clock genes are disrupted in melanoma and linked to immune escape. Herein, we found that the expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated in melanoma patients and that patients with higher RORA expression have a better prognosis after immunotherapy. Additionally, RORA was significantly positively correlated with T-cell infiltration and recruitment. Overexpression or activation of RORA stimulated cytotoxic T-cell-mediated antitumor responses. RORA bound to the CD274 promoter and formed an inhibitory complex with HDAC3 to suppress PD-L1 expression. In contrast, the DEAD-box helicase family member DDX3X competed with HDAC3 for binding to RORA, and DDX3X overexpression promoted RORA release from the suppressive complex and thereby increased PD-L1 expression to generate an inhibitory immune environment. The combination of a RORA agonist with an anti-CTLA4 antibody synergistically increased T-cell antitumor immunity in vivo. A score based on the combined expression of HDAC3, DDX3X, and RORA correlated with immunotherapy response in melanoma patients. Together, this study elucidates a mechanism of clock component-regulated antitumor immunity, which will help inform the use of immunotherapy and lead to improved outcomes for melanoma patients receiving combined therapeutic treatments. Significance: RORA forms a corepressor complex to inhibit PD-L1 expression and activate antitumor T-cell responses, indicating that RORA is a potential target and predictive biomarker to improve immunotherapy response in melanoma patients.
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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 Socratic graph.