免疫系统
癌症研究
头颈部鳞状细胞癌
炎症
肿瘤微环境
免疫检查点
癌症
转录组
免疫疗法
生物
癌细胞
免疫学
头颈部癌
基因表达
基因
生物化学
遗传学
作者
Chih-Hung Chung,Chun-Yu Lin,Chih-Yu Chen,Chun-Wei Hsueh,Yao‐Wen Chang,Chen‐Chi Wang,Pen‐Yuan Chu,Shyh–Kuan Tai,Muh Hwa Yang
标识
DOI:10.1002/advs.202204514
摘要
As a type of immunogenic cell death, ferroptosis participates in the creation of immunoactive tumor microenvironments. However, knowledge of spatial location of tumor cells with ferroptosis signature in tumor environments and the role of ferroptotic stress in inducing the expression of immune-related molecules in cancer cells is limited. Here the spatial association of the transcriptomic signatures is demonstrated for ferroptosis and inflammation/immune activation located in the invasive front of head and neck squamous cell carcinoma (HNSCC). The association between ferroptosis signature and inflammation/immune activation is more prominent in HPV-negative HNSCC compared to HPV-positive ones. Ferroptotic stress induces PD-L1 expression through reactive oxygen species (ROS)-elicited NF-κB signaling pathway and calcium influx. Priming murine HNSCC with the ferroptosis inducer sensitizes tumors to anti-PD-L1 antibody treatment. A positive correlation between the ferroptosis signature and the active immune cell profile is shown in the HNSCC samples. This study reveals a subgroup of ferroptotic HNSCC with immune-active signatures and indicates the potential of priming HNSCC with ferroptosis inducers to increase the antitumor efficacy of immune checkpoint inhibitors.
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