ArticleNature communications2022
USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Epigenetic regulation of major histocompatibility complexes in gastrointestinal malignancies and the potential for clinical interception.Clinical epigenetics · 2024Pooled it
- A USP8-targeting nanoamplifier synergizes with radiotherapy to remodel the immunosuppressive tumor microenvironment in lung cancer.Materials today. Bio · 2026Article
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- Article
- Targeting the NAT1-ENO1-Lactate Axis Destabilizes PD-L1 to Reinvigorate Antitumor Immunity in Colorectal Cancer.MedComm · 2026Article
- SIRT2-mediated deacetylation activates USP22 catalytic function for PD-L1 protein stabilization and tumor immune escape.The Journal of clinical investigation · 2026Article
- Enhancing immunotherapy efficacy of hepatocellular carcinoma by inhibiting the key antioxidant factor Nrf2.Molecular therapy. Oncology · 2026Article
- USP21 drives immune evasion in colorectal cancer via deubiquitination and stabilization of β-catenin.Cellular & molecular immunology · 2026Article
- The value of targeting CXCR4 withEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Targeting PSMD14 enhances immunotherapy efficacy by promoting PD-L1 degradation and reshaping the tumor microenvironment in breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- K48 and K63 linkage-competed ubiquitination of BECN1 promotes circPDE4D-mediated autophagy in chronic obstructive pulmonary disease.Cell death & disease · 2026Article
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 2026Article
- Endothelial USP8 is essential for angiogenesis.Angiogenesis · 2026Article
- Positive feedback regulation between USP8 and Hippo/YAP axis drives triple-negative breast cancer progression.Cell death & disease · 2026Article
- Targeting the N-acetyltransferase 10/DKK2 axis enhances CD8+ T cell antitumor activity in colorectal cancer models.The Journal of clinical investigation · 2026Article
- USP8-mediated mitochondrial regulation in osteoclasts is essential for skeletal development.Cellular and molecular life sciences : CMLS · 2026Article
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- Advances in protein ubiquitination modification and immune evasion of breast cancer.Frontiers in cell and developmental biology · 2026Review
- High expression of USP15 affects tumor progression and immune infiltration in hepatocellular carcinoma.Hepatology forum · 2026Article
- Targeting Mitochondrial PD-L1 O-GlcNAcylation to Sensitize HBV-Related HCC to Immunotherapy: Modulating Golgi-mitochondrial Crosstalk and mTOR/PGC-1α-Driven Mitochondrial Biogenesis to Overcome Resistance.International journal of biological sciences · 2026Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
Abstract
Anti-PD-1/PD-L1 immunotherapy has achieved impressive therapeutic outcomes in patients with multiple cancer types. However, the underlined molecular mechanism(s) for moderate response rate (15-25%) or resistance to PD-1/PD-L1 blockade remains not completely understood. Here, we report that inhibiting the deubiquitinase, USP8, significantly enhances the efficacy of anti-PD-1/PD-L1 immunotherapy through reshaping an inflamed tumor microenvironment (TME). Mechanistically, USP8 inhibition increases PD-L1 protein abundance through elevating the TRAF6-mediated K63-linked ubiquitination of PD-L1 to antagonize K48-linked ubiquitination and degradation of PD-L1. In addition, USP8 inhibition also triggers innate immune response and MHC-I expression largely through activating the NF-κB signaling. Based on these mechanisms, USP8 inhibitor combination with PD-1/PD-L1 blockade significantly activates the infiltrated CD8
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Registered trials
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.