肿瘤微环境
免疫系统
巨噬细胞极化
巨噬细胞
肿瘤进展
肺癌
免疫学
血管生成
癌症
生物
癌症免疫疗法
癌细胞
癌症研究
医学
免疫疗法
病理
体外
生物化学
遗传学
作者
Bufu Tang,Yajie Wang,Wangting Xu,Jinyu Zhu,Qiaoyou Weng,Weiqian Chen,Shiji Fang,Yang Yang,Rongfang Qiu,Minjiang Chen,Weiyang Mao,Min Xu,Zhongwei Zhao,Songhua Cai,Hongbing Zhang,Jiansong Ji
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-02-01
卷期号:554: 216021-216021
被引量:15
标识
DOI:10.1016/j.canlet.2022.216021
摘要
Tumor-associated macrophages (TAMs) play an important role in remodeling the tumor microenvironment (TME), which promotes tumor growth, immunosuppression and angiogenesis. Because of the high plasticity of macrophages and the extremely complex tumor microenvironment, the mechanism of TAMs in cancer progression is still largely unknown. In this study, we found that xCT (SLC7A11) was overexpressed in lung cancer-associated macrophages. Higher xCT in TAMs was associated with poor prognosis and was an independent predictive factor in lung cancer. In addition, lung cancer growth and progression was inhibited in xCT knockout mice, especially macrophage-specific xCT knockout mice. We also found that the deletion of macrophage xCT inhibited AKT/STAT6 signaling activation and reduced M2-type polarization of TAMs. Macrophage xCT deletion recruited more CD8+ T cells and activated the lung cancer cell-mediated and IFN-γ-induced JAK/STAT1 axis and increased the expression of its target genes, including CXCL10 and CD274. The combination of macrophage xCT deletion and anti-PDL1 antibody achieved better tumor inhibition. Finally, combining the xCT inhibitor erastin with an anti-PDL1 antibody was more potent in inhibiting lung cancer progression. Therefore, suppression of xCT may overcome resistance to cancer immunotherapy.
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