ArticleJournal of translational medicine2023
ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- ISGylation-mediated stabilization of CYP4Z1 fuels breast cancer initiation and progression.Experimental & molecular medicine · 2026Article
- Comprehensive analysis ofJournal of thoracic disease · 2026Article
- Article
- The ubiquitin-like protein FAT10 enhances the autophagy-mediated degradation of ZO-1 by stabilizing ATG3 to promote the lung metastasis of colon cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- ISGylation prevents autophagic degradation of STING and promotes antitumor immunity in lung cancer.Cell death & disease · 2026Article
- ISG15-driven immune modulation and tumor progression in breast cancer metastasis: insights from single-cell and spatial transcriptomics.BMC medicine · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- Spermidine reduces ISGylation and enhances ISG15-USP18 interaction.Scientific reports · 2025Article
- Multi-Omics Analysis of the Epigenetic Effects of Inflammation in Murine Type II Pneumocytes.International journal of molecular sciences · 2025Article
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025Review
- HERC5/ISG15 Enhances Glioblastoma Stemness and Tumor Progression by mediating SERBP1protein stability.Neuromolecular medicine · 2025Article
- The role of glycan-lectin interactions in the tumor microenvironment: immunosuppression regulators of colorectal cancer.American journal of cancer research · 2025Review
- Resolving tumor microenvironment heterogeneity to forecast immunotherapy response in triple-negative breast cancer through multi-scale analysis.Frontiers in oncology · 2025Article
- Article
- Integrative multi-omics reveals energy metabolism-related prognostic signatures and immunogenetic landscapes in lung adenocarcinoma.Frontiers in immunology · 2025Article
- A Comprehensive Pan-cancer Analysis Identified that TRIB3 was Associated with Immune Cell Infiltration and Poor Prognosis.Current pharmaceutical biotechnology · 2025Article
- USP18 Is Associated with PD-L1 Antitumor Immunity and Improved Prognosis in Colorectal Cancer.Biomolecules · 2024Article
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown.
methodsThe relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues.
resultsISG15 promotes the infiltration of CD4
conclusionsThe ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy.
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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 OpenQuestion graph.