SCI

21 July 2024

The balance of STING signaling orchestrates immunity in cancer

(Nature immunology;IF:27.7)

  • Lanng KRB, Lauridsen EL, Jakobsen MR. The balance of STING signaling orchestrates immunity in cancer. Nat Immunol. 2024 Jul;25(7):1144-1157. doi: 10.1038/s41590-024-01872-3. Epub 2024 Jun 25. PMID: 38918609.

  • Corresponding author:Martin Roelsgaard Jakobsen, Department of Biomedicine, Aarhus University, Aarhus, Denmark.  e-mail: mrj@biomed.au.dk

Abstract 摘要

Over the past decade, it has become clear that the stimulator of interferon genes (STING) pathway is critical for a variety of immune responses. This endoplasmic reticulum-anchored adaptor protein has regulatory functions in host immunity across a spectrum of conditions, including infectious diseases, autoimmunity, neurobiology and cancer. In this Review, we outline the central importance of STING in immunological processes driven by expression of type I and III interferons, as well as inflammatory cytokines, and we look at therapeutic options for targeting STING. We also examine evidence that challenges the prevailing notion that STING activation is predominantly beneficial in combating cancer. Further exploration is imperative to discern whether STING activation in the tumor microenvironment confers true benefits or has detrimental effects. Research in this field is at a crossroads, as a clearer understanding of the nuanced functions of STING activation in cancer is required for the development of next-generation therapies.

在过去的十年里,已经明确干扰素基因刺激因子(STING)通路对于各种免疫反应至关重要。这个锚定于内质网的适配蛋白在包括传染病、自身免疫、神经生物学和癌症等多种条件下具有调节宿主免疫的功能。在这篇综述中,我们概述了STING在通过I型和III型干扰素以及炎性细胞因子表达驱动的免疫过程中的核心重要性,并探讨了靶向STING的治疗选择。我们还审视了质疑STING激活主要在抗癌方面有利的现有观点的证据。进一步的探索对于辨别肿瘤微环境中STING激活是否真正有益或有害至关重要。这个领域的研究正处于一个关键节点,因为对于STING激活在癌症中详细作用的更清晰理解是开发下一代疗法所必需的。