ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1625226
This article is part of the Research TopicCommunity Series in Methods in Cancer Immunity and Immunotherapy: Volume IIView all 8 articles
Urokinase-type plasminogen activator deficiency enhances CD8 + T cell infiltration and anti-PD-1 therapy efficacy in prostate cancer
Provisionally accepted
- 1Southern University of Science and Technology, Shenzhen, China
- 2Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, China
- 3Guangzhou Concord Cancer Center, Gunagzhou, China
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This study investigates the urokinase-type plasminogen activator (uPA) as a key immunosuppressive regulator in prostate cancer. We reveal uPA deficiency enhances antitumor immunity and therapeutic potential for the combination of uPA inhibitor and immune checkpoint blockade. Here, we identify elevated uPA expression in clinical prostate cancer specimens, with inverse correlation to CD8 + T cell infiltration. Genetic ablation (uPA -/-mice) and pharmacological inhibition (UK122) of uPA significantly attenuate tumor growth via strengthening antitumor immunity. CyTOF analysis and flow cytometry show that uPA deficiency strongly enhances the CD8 + T cell infiltration. uPA -/-CD8 + T cell engineered with anti-CD19 chimeric antigen receptor (CAR) exhibits enhanced cytotoxicity compared to wild-type controls. Notably, a higher percentage of uPA -/-CD8 + T cell express PD-1, and UK122 synergizes with anti-PD-1 therapy to boost tumor regression. This suggests that targeting uPA may be a novel approach to enhance immunotherapy effectiveness for prostate cancer.
Keywords: Urokinase-Type Plasminogen Activator, prostate cancer, CD8 + T cell, Tumor immune microenvironment, combination therapy
Received: 08 May 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 LI, Zhang, Fu, Wu, Ye, Huang, Cui, Qian, Lu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyi LI, Southern University of Science and Technology, Shenzhen, China
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