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探索蛋白质乳酰化在前列腺癌中的作用及其对免疫治疗的影响。

Navigating the role of protein lactylation in prostate cancer and its implications for immunotherapy.

作者信息

Li Dongzhang, Wang Kaifeng, Lou Guantao, Li Wangjian, Ma Quan, Liu Yu'e, Chen Yongliang

机构信息

Dept of Urology, Shaoxing Central Hospital, Shaoxing, Zhejiang, 312030, China.

Dept of Urology, The Central Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, 312030, China.

出版信息

J Cancer. 2025 Jun 12;16(8):2706-2719. doi: 10.7150/jca.114137. eCollection 2025.

Abstract

Prostate cancer is an aggressive malignancy with high prevalence and significant mortality, characterized by its remarkable metabolic adaptability and immune complexity. Emerging evidence has highlighted the critical role of post-translational modifications (PTMs) in cancer biology, with protein lactylation gaining attention as a novel PTM with profound implications. Lactylation, derived from lactate, links the altered metabolic processes of tumor cells to diverse cellular functions, including epigenetic regulation and protein dynamics. It significantly influences tumor progression, immune evasion, and therapeutic resistance by modulating key immune cells within the tumor microenvironment. The immunosuppressive conditions created by lactate and lactylation favor tumor survival in prostate cancer. Thus, targeting lactylation offers innovative strategies for treating prostate cancer. By leveraging lactylation modulation, particularly in combination with immune checkpoint inhibitors, there is potential to enhance anti-tumor immune responses and improve treatment outcomes. This review explores the intersection of metabolic alterations and immune modulation, underscoring lactylation as a promising therapeutic avenue in prostate cancer.

摘要

前列腺癌是一种侵袭性恶性肿瘤,具有高发病率和显著死亡率,其特征在于具有显著的代谢适应性和免疫复杂性。新出现的证据凸显了翻译后修饰(PTM)在癌症生物学中的关键作用,蛋白质乳酰化作为一种具有深远影响的新型PTM受到关注。乳酰化由乳酸衍生而来,将肿瘤细胞改变的代谢过程与多种细胞功能联系起来,包括表观遗传调控和蛋白质动态变化。它通过调节肿瘤微环境中的关键免疫细胞,显著影响肿瘤进展、免疫逃逸和治疗抗性。乳酸和乳酰化产生的免疫抑制条件有利于前列腺癌中的肿瘤存活。因此,靶向乳酰化为治疗前列腺癌提供了创新策略。通过利用乳酰化调节,特别是与免疫检查点抑制剂联合使用,有可能增强抗肿瘤免疫反应并改善治疗效果。本综述探讨了代谢改变与免疫调节的交叉点,强调乳酰化是前列腺癌中一个有前景的治疗途径。

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