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Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).

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Oncology reports 📖 저널 OA 88.8% 2022: 2/2 OA 2024: 5/5 OA 2025: 33/35 OA 2026: 71/75 OA 2022~2026 2025 Vol.54(6)
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Gu LH, Guo A, Ding YY, Wang XJ, Zhang HX, Duan WL

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Cancer cells play a pivotal role in immune evasion by activating the programmed cell death protein 1 (PD‑1)/PD‑ligand (L)1 signaling pathway or immune cells within the tumor microenvironment.

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APA Gu LH, Guo A, et al. (2025). Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).. Oncology reports, 54(6). https://doi.org/10.3892/or.2025.9000
MLA Gu LH, et al.. "Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).." Oncology reports, vol. 54, no. 6, 2025.
PMID 41041864 ↗

Abstract

Cancer cells play a pivotal role in immune evasion by activating the programmed cell death protein 1 (PD‑1)/PD‑ligand (L)1 signaling pathway or immune cells within the tumor microenvironment. The ubiquitin‑proteasome system (UPS), the primary pathway for intracellular protein degradation, has been increasingly implicated in mediating tumor immune escape and resistance to anti‑PD‑1/PD‑L1 therapy. Targeting the UPS has demonstrated significant potential in improving the efficacy of tumor immunotherapy. Therefore, a deeper understanding of the molecular mechanisms by which UPS contributes to tumor resistance against PD‑1/PD‑L1 blockade, along with the optimization of UPS‑targeted small‑molecule drug design, holds scientific and clinical significance. In the present review, the role of UPS in tumor immune evasion through the regulation of PD‑1/PD‑L1 ubiquitination was discussed and potential therapeutic agents that may enhance the effectiveness of anti‑PD‑1/PD‑L1 treatment are summarized. These insights provide a theoretical foundation for advancing cancer immunotherapy and developing novel combination strategies.

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