School of Mechanical and Materials Engineering, Engineering and Materials Science Centre, University College Dublin, Dublin, Ireland.
University College Dublin (UCD) Centre for Biomedical Engineering, University College Dublin, Belfield Dublin, Ireland.
Front Immunol. 2024 Sep 30;15:1403538. doi: 10.3389/fimmu.2024.1403538. eCollection 2024.
Osteosarcoma is a highly aggressive bone cancer primarily affecting children, adolescents, and young adults. The current gold standard for treatment of osteosarcoma patients consists of two to three rounds of chemotherapy, followed by extensive surgical intervention from total limb reconstruction to amputation, followed by additional rounds of chemotherapy. Although chemotherapy has advanced the treatment of osteosarcoma significantly, the overall 5-year survival rate in resistant forms of osteosarcoma is still below 20%. The interaction between cancer and the immune system has long been recognized as a critical aspect of tumour growth. Tumour cells within the tumour microenvironment (TME) suppress antitumour immunity, and immunosuppressive cells and cytokines provide the extrinsic factors of tumour drug resistance. Emerging research demonstrates an immunostimulatory role for the cGAS/STING pathway in osteosarcoma, typically considered an immune-cold or immunosuppressed cancer type. cGAS/STING signalling appears to drive an innate immune response against tumours and potentiates the efficacy of other common therapies including chemo and radiotherapy. Nanotechnological delivery systems for improved therapy delivery for osteosarcoma have also been under investigation in recent years. This review provides an overview of cGAS/STING signalling, its divergent roles in the context of cancer, and collates current research which activates cGAS/STING as an adjuvant immunomodulatory target for the treatment of osteosarcoma. It will also discuss current nanotechnological delivery approaches that have been developed to stimulate cGAS/STING. Finally, it will highlight the future directions that we believe will be central to the development of this transformative field.
骨肉瘤是一种高度侵袭性的骨癌，主要影响儿童、青少年和年轻成年人。目前，骨肉瘤患者的治疗金标准包括两到三轮化疗，随后进行广泛的手术干预，从全肢重建到截肢，然后再进行更多轮的化疗。尽管化疗显著改善了骨肉瘤的治疗效果，但在耐药性骨肉瘤形式中，总体 5 年生存率仍低于 20%。癌症与免疫系统的相互作用长期以来一直被认为是肿瘤生长的关键方面。肿瘤细胞在肿瘤微环境（TME）中抑制抗肿瘤免疫，而免疫抑制细胞和细胞因子提供了肿瘤耐药的外在因素。新兴研究表明，cGAS/STING 通路在骨肉瘤中具有免疫刺激作用，通常被认为是一种免疫冷或免疫抑制性癌症类型。cGAS/STING 信号似乎驱动了针对肿瘤的先天免疫反应，并增强了其他常见疗法（包括化疗和放疗）的疗效。近年来，也一直在研究用于改善骨肉瘤治疗的纳米技术递送系统。本综述概述了 cGAS/STING 信号，及其在癌症背景下的不同作用，并整理了目前将激活 cGAS/STING 作为骨肉瘤治疗的辅助免疫调节靶点的研究。它还将讨论已经开发出来刺激 cGAS/STING 的当前纳米技术递送方法。最后，它将强调我们认为对这一变革性领域的发展至关重要的未来方向。
