ArticleThe Journal of clinical investigation2023
UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Mapping research trends in macrophage polarization and immunotherapeutic potential in prostate cancer: a bibliometric and visual analysis.Frontiers in oncology · 2026Pooled it
- Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Ubc9-mediated SUMOylation of Ninj1 alleviates inflammatory responses in hepatic ischaemia/reperfusion injury.Clinical and translational medicine · 2026Article
- Fludarabine disrupts the STAT1/AhR interaction to attenuate type 1 diabetes by inducing tolerogenic dendritic cells along with targeting effector T cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- UBC9-mediated SUMOylation of CORO1C drives lung adenocarcinoma progression via Arp2/3-dependent cytoskeletal remodeling.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
- UBC9-mediated regulation of K144 ubiquitination of Lamin A and its implications for hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- Ubc9-Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9-p16 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting IQGAP3 skews macrophages polarization towards M1 phenotype and promotes antitumor immune response.Cellular and molecular life sciences : CMLS · 2025Article
- UBC9 mediates mitophagy to attenuate oxidative stress by regulating SUMOylation of PINK1 in the Parkinson's disease progression.Cell biology and toxicology · 2025Article
- Positive and negative roles of myeloid cells in cancer immunotherapy.Journal for immunotherapy of cancer · 2025Review
- Targeted deprivation of STAT6 sensitizes acute lymphoblastic leukemia cells to cytarabine in vivo and in vitro: clinical implications.Cell death & disease · 2025Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- SUMOylation is a Translatable Target in Hypoxic MNPs Regulating Retinal Vasculopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The co-location of MARCO+ tumor-associated macrophages and CTSE+ tumor cells determined the poor prognosis in intrahepatic cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2025Article
- Bolstering CD8Biology · 2025Review
- SENP1-mediated deSUMOylation of YBX1 promotes colorectal cancer development through the SENP1-YBX1-AKT signaling axis.Oncogene · 2025Article
- UBC9: a novel therapeutic target in papillary thyroid carcinoma.Journal of endocrinological investigation · 2025Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented CD8+ T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on CD8+ T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage-CD8+ T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis.
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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.