肿瘤微环境
癌症研究
刺
刺激
髓样
化学
细胞
医学
生物
内科学
生物化学
肿瘤细胞
工程类
航空航天工程
作者
Blake R. Heath,Wang Gong,Hülya F. Taner,Luke J. Broses,Kazuaki Okuyama,Weiming Cheng,Max Jin,Zackary R. Fitzsimonds,Andriana Manousidaki,Yuesong Wu,Shaoping Zhang,Haitao Wen,Steven B. Chinn,Eric Bartee,Yuying Xie,James J. Moon,Yu Lei
出处
期刊:Cell Reports
[Elsevier]
日期:2023-04-01
卷期号:42 (4): 112303-112303
被引量:6
标识
DOI:10.1016/j.celrep.2023.112303
摘要
Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show dampened responses to STING stimulation and are more suppressive of T cell activation. In agreement, obese hosts exhibited increased tumor burden and lower responsiveness to STING agonist. As a mechanism, saturated fatty acids induce the expression of NLRC3, depletion of which results in a T cell inflamed tumor microenvironment and IFN-I-dependent tumor control.
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