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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1470468
This article is part of the Research Topic Innate Immune Pathways as Targets for Developing Therapeutic Intervention against Human Cancers View all 4 articles

Bidirectional regulation of the cGAS-STING pathway in the immunosuppressive tumor microenvironment and its association with immunotherapy

Provisionally accepted
Yurui Zhang Yurui Zhang 1Yudi Wang Yudi Wang 1Peizheng Mu Peizheng Mu 2Xiao Zhu Xiao Zhu 2*Yucui Dong Yucui Dong 1*
  • 1 Department of Immunology, Binzhou Medical University, Binzhou, China
  • 2 School of Computer and Control Engineering, Yantai University, Yantai, Shandong Province, China

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

    Adaptive anti-tumor immunity is currently dependent on the natural immune system of the body. The emergence of tumor immunotherapy has improved prognosis and prolonged the survival cycle of patients. Current mainstream immunotherapies, including immune checkpoint blockade, chimeric antigen receptor T-cell immunotherapy, and monoclonal antibody therapy, are linked to natural immunity.The cGAS-STING pathway is an important natural immunity signaling pathway that plays an important role in fighting against the invasion of foreign pathogens and maintaining the homeostasis of the organism. Increasing evidence suggests that the cGAS-STING pathway plays a key role in tumor immunity, and the combination of STING-related agonists can significantly enhance the efficacy of immunotherapy and reduce the emergence of immunotherapeutic resistance. However, the cGAS-STING pathway is a double-edged sword, and its activation can enhance anti-tumor immunity and immunosuppression. Immunosuppressive cells, including M2 macrophages, MDSC, and regulatory T cells, in the tumor microenvironment play a crucial role in tumor escape, thereby affecting the immunotherapy effect. The cGAS-STING signaling pathway can bi-directionally regulate this group of immunosuppressive cells, and targeting this pathway can affect the function of immunosuppressive cells, providing new ideas for immunotherapy. In this study, we summarize the activation pathway of the cGAS-STING pathway and its immunological function and elaborate on the key role of this pathway in immune escape mediated by the tumor immunosuppressive microenvironment. Finally, we summarize the mainstream immunotherapeutic approaches related to this pathway and explore ways to improve them, thereby providing guidelines for further clinical services.

    Keywords: ： cGAS-STING, tumor, TME, Immunotherapy, immune escape

    Received: 25 Jul 2024; Accepted: 25 Sep 2024.

    Copyright: © 2024 Zhang, Wang, Mu, Zhu and Dong. 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:
    Xiao Zhu, School of Computer and Control Engineering, Yantai University, Yantai, 264005, Shandong Province, China
    Yucui Dong, Department of Immunology, Binzhou Medical University, Binzhou, China

    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.