头颈部鳞状细胞癌
多西紫杉醇
肿瘤微环境
癌症研究
分泌物
巨噬细胞
化学
生物
医学
内科学
癌症
头颈部癌
体外
生物化学
肿瘤细胞
作者
Ching-Yun Hsieh,Chih-Hung Lin,Yuesheng Huang,Jong-Hang Chen,Yung‐An Tsou,Ling‐Chu Chang,Chi-Chen Fan,Chen‐Yuan Lin,Wei‐Chao Chang
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2022-12-08
卷期号:7 (23)
被引量:10
标识
DOI:10.1172/jci.insight.157285
摘要
Docetaxel (DTX) combined with cisplatin and 5-fluorouracil has been used as induction chemotherapy for head and neck squamous cell carcinoma (HNSCC). However, the development of acquired resistance remains a major obstacle to treatment response. Tumor-associated macrophages are associated with chemotherapeutic resistance. In the present study, increased infiltration of macrophages into the tumor microenvironment (TME) was significantly associated with shorter overall survival and increased resistance to chemotherapeutic drugs, particularly DTX, in patients with HNSCC. Macrophage coculture induced expression of intercellular adhesion molecule 1 (ICAM1), which promotes stemness and the formation of polyploid giant cancer cells, thereby reducing the efficacy of DTX. Both genetic silencing and pharmacological inhibition of ICAM1 sensitized HNSCC to DTX. Macrophage secretion of IL-1β was found to induce tumor expression of ICAM1. IL-1β neutralization and IL-1 receptor blockade reversed DTX resistance induced by macrophage coculture. IL-1β activated superoxide dismutase 2 and inhibited catalase, thereby modulating intracellular levels of ROS and inducing ICAM1 expression. Arsenic trioxide (ATO) reduced macrophage infiltration into the TME and impaired IL-1β secretion by macrophages. The combinatorial use of ATO enhanced the in vivo efficacy of DTX in a mouse model, which may provide a revolutionary approach to overcoming acquired therapeutic resistance in HNSCC.
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