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Citations to this article

UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer
Jun Xiao, … , Cong-Yi Wang, Zhi-Hua Wang
Jun Xiao, … , Cong-Yi Wang, Zhi-Hua Wang
Published January 10, 2023
Citation Information: J Clin Invest. 2023;133(4):e158352. https://doi.org/10.1172/JCI158352.
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Research Article Immunology Oncology Article has an altmetric score of 1

UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer

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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.

Authors

Jun Xiao, Fei Sun, Ya-Nan Wang, Bo Liu, Peng Zhou, Fa-Xi Wang, Hai-Feng Zhou, Yue Ge, Tian-Tian Yue, Jia-Hui Luo, Chun-Liang Yang, Shan-Jie Rong, Ze-Zhong Xiong, Sheng Ma, Qi Zhang, Yang Xun, Chun-Guang Yang, Yang Luan, Shao-Gang Wang, Cong-Yi Wang, Zhi-Hua Wang

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Total citations by year

Year: 2025 2024 2023 Total
Citations: 8 13 5 26
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2023 (5)

Title and authors Publication Year
SUMOylation of RNF146 results in Axin degradation and activation of Wnt/β-catenin signaling to promote the progression of hepatocellular carcinoma.
Li W, Han Q, Zhu Y, Zhou Y, Zhang J, Wu W, Li Y, Liu L, Qiu Y, Hu K, Yin D
Oncogene 2023
The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.
Gu Y, Fang Y, Wu X, Xu T, Hu T, Xu Y, Ma P, Wang Q, Shu Y
Experimental Hematology and Oncology 2023
The Prognosis-Predictive and Immunoregulatory Role of SUMOylation Related Genes: Potential Novel Targets in Prostate Cancer Treatment
Sun JX, An Y, Xiang JC, Xu JZ, Hu J, Wang SG, Xia QD
International journal of molecular sciences 2023
STAT4 facilitates PD‐L1 level via IL‐12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer
Zhou J, Wan F, Wang L, Peng C, Huang R, Peng F
2023
Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer.
Ge Y, Ma S, Zhou Q, Xiong Z, Wang Y, Li L, Chao Z, Zhang J, Li T, Wu Z, Gao Y, Qu G, Xi Z, Liu B, Wu X, Wang Z
Chinese medical journal 2023

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Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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