ArticleCell death discovery2023
RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Integrated multi-omics and single-cell analysis of galectins and immune associations in triple-negative breast cancer.Translational oncology · 2026Article
- Expression, Localization and Actions of Galectin-3: Implications in the Pathophysiology and Therapy of Cardiovascular Disease.International journal of molecular sciences · 2026Review
- Galectin-3 promotes FBXL5-dependent ubiquitination and degradation of YAP1 to constrain colorectal cancer growth.Frontiers in immunology · 2026Article
- The RNF8/OPTN/KDM6A axis controls macrophage polarization to maintain testicular microenvironment homeostasis.Cell death discovery · 2025Article
- A pH/MMP-9 smart dual-responsive liposome GBE@LP co-delivers and controls the release of GB1107/BMS1166/Enzalutamide for liver cancer immunotherapy.Materials today. Bio · 2025Article
- Crotonylation of MCM6 enhances chemotherapeutics sensitivity of breast cancer via inducing DNA replication stress.Cell proliferation · 2025Article
- Selective Glycopolymer Inhibitors of Galectin-3: Supportive Anti-Cancer Agents Protecting Monocytes and Preserving Interferon-Gamma Function.International journal of nanomedicine · 2025Article
- NPRL2 promotes TRIM16-mediated ubiquitination degradation of Galectin-3 to prevent CD8Cellular and molecular life sciences : CMLS · 2024Article
- N-Acetylgalactosamine-4-sulfatase (Arylsulfatase B) Regulates PD-L1 Expression in Melanoma by an HDAC3-Mediated Epigenetic Mechanism.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The failure of melanoma immunotherapy can be mediated by immunosuppression in the tumor microenvironment (TME), and insufficient activation of effector T cells against the tumor. Here, we show that inhibition of galectin-3 (gal-3) enhances the infiltration of T cells in TME and improves the sensitivity of anti-PD-L1 therapy. We identify that RNF8 downregulated the expression of gal-3 by K48-polyubiquitination and promoted gal-3 degradation via the ubiquitin-proteasome system. RNF8 deficiency in the host but sufficiency in implanted melanoma results in immune exclusion and tumor progression due to the upregulation of gal-3. Upregulation of gal-3 decreased the immune cell infiltration by restricting IL-12 and IFN-γ. Inhibition of gal-3 reverses immunosuppression and induces immune cell infiltration in the tumor microenvironment. Moreover, gal-3 inhibitor treatment can increase the sensitivity of PD-L1 inhibitors via increasing immune cell infiltration and enhancing immune response in tumors. This study reveals a previously unrecognized immunoregulation function of RNF8 and provides a promising strategy for the therapy of "cold" tumors. Tremendous effects of melanoma treatment can be achieved by facilitating immune cell infiltration combined with anti-PD-L1 treatment.
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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.