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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1403538
This article is part of the Research Topic Advances in Immunotherapy in Pediatric Solid Tumors View all 4 articles

Make it STING: Nanotechnological approaches for activating cGAS/STING as an immunomodulatory node in osteosarcoma

Provisionally accepted
Jordan C. O'Donoghue Jordan C. O'Donoghue 1,2,3Fiona E. Freeman Fiona E. Freeman 1,2,3,4,5,6*
  • 1 School of Mechanical and Materials Engineering, Engineering and Materials Science Centre, University College Dublin, Dublin, County Dublin, Ireland
  • 2 UCD Centre for Biomedical Engineering, University College Dublin,, Dublin, Ireland
  • 3 Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
  • 4 Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
  • 5 Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Dublin, County Dublin, Ireland
  • 6 Advanced Materials and BioEngineering Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland

The final, formatted version of the article will be published soon.

    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.

    Keywords: cGAS1, STING2, immunotherapy3, innate immunity4, Nanotechnology5, Drug Delivery6, Osteosarcoma7

    Received: 19 Mar 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 O'Donoghue and Freeman. 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: Fiona E. Freeman, School of Mechanical and Materials Engineering, Engineering and Materials Science Centre, University College Dublin, Dublin, Dublin 4, County Dublin, Ireland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.