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干扰素基因刺激因子(STING)的激活:克服前列腺癌免疫抵抗的有前景策略

英文原题:Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

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Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

PubMed 2024/01/01(内容时间) Curr Med Chem Q2 · IF 3.2(JCR 2025)

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中文摘要

前列腺癌(PCa)是男性中最常见且致死率位居第二的癌症。尽管在探索自体细胞免疫治疗和免疫检查点抑制剂等疗法方面付出了相当大的努力,但其成功率仍然有限。复杂的肿瘤微环境(TME)及其与免疫系统的相互作用给PCa治疗带来了重大挑战。

因此,研究人员将焦点转向通过靶向干扰素基因刺激因子(STING)通路来增强免疫系统的抗肿瘤反应。当在先天免疫细胞胞质中检测到外源DNA时,STING通路被激活,导致内质网(ER)中STING的激活。这反过来触发信号增强,导致I型干扰素(IFN)和其他促炎细胞因子的产生。大量研究表明,STING通路的激活可诱导免疫系统排斥并靶向清除PCa细胞。研究人员一直在探索激活STING通路的多种方法,包括使用细菌载体递送STING激动剂以及将放射治疗与STING激动剂联合使用。要实现副作用最小且抗肿瘤免疫反应最佳的有效放射治疗,必须精确调整放射剂量和分割方案。这篇综合性综述讨论了聚焦于激活STING通路以对抗PCa的研究中令人鼓舞的发现。STING通路展现出作为PCa有效治疗模式的潜力,为改善受这种毁灭性疾病影响的患者生活带来了新希望。

展开英文摘要原文

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines.

Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists.

Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.

论文信息

作者
Alnukhali M、Altabbakh O、Farooqi AA、Pollack A、Daunert S、Deo S、Tao W
第一作者单位
Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.United States
通讯作者单位
Department of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.United States
文献类型
综述
期刊
Current medicinal chemistry2024
原文标识
PubMed 38347787 · DOI 10.2174/0109298673273303231208071403