ArticleCancer immunology, immunotherapy : CII2021
Identification of STXBP6-IRF1 positive feedback loop in regulation of PD-L1 in cancer.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- STXBP6 regulates growth, metastasis and lipid metabolism of ovarian cancer cells via the PI3K/AKT signaling pathway.Medical oncology (Northwood, London, England) · 2025Article
- Insight into the shared pathogenic link between COVID-19 and pterygium: a systematic bioinformatics analysis with experimental validation.Hereditas · 2025Article
- Roles of Interferon Regulatory Factor 1 in Tumor Progression and Regression: Two Sides of a Coin.International journal of molecular sciences · 2024Review
- DPEP1 promotes drug resistance in colon cancer cells by forming a positive feedback loop with ASCL2.Cancer medicine · 2023Article
- Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target againstScience advances · 2022Article
- The upregulation ofFrontiers in oncology · 2022Article
- Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- circ_0002346 Suppresses Non-Small-Cell Lung Cancer Progression Depending on the Regulation of the miR-582-3p/STXBP6 Axis.International journal of genomics · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
The clinical success of immune checkpoint blockade against diverse human cancers highlights the critical importance of insightful understanding into mechanisms underlying PD-L1 regulation. IFN-γ released by intratumoral lymphocytes regulates PD-L1 expression in tumor cells through JAK-STAT-IRF1 pathway, while the molecular events prime IRF1 to translocate into nucleus are still obscure. Here we identified STXBP6, previously recognized involving in SNARE complex assembly, negatively regulates PD-L1 transcription via retention of IRF1 in cytoplasm. IFN-γ exposure stimulates accumulation of cytosolic IRF1, which eventually saturates STXBP6 and triggers nuclear translocation of IRF1. Nuclear IRF1 in turn inhibits STXBP6 expression and thereby liberates more IRF1 to migrate to nucleus. Therefore, we identified a novel positive feedback loop between STXBP6 and IRF1 in regulation of PD-L1 expression in cancer. Furthermore, we demonstrate STXBP6 overexpression significantly inhibits T cell activation both in vitro and in vivo. These findings offer new insight into the complexity of PD-L1 expression in cancer and suggest a valuable measure to predict the response to PD-1/PD-L1-based immunotherapy.
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Registered trials
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