免疫监视
生物
头颈部鳞状细胞癌
癌症干细胞
癌症研究
免疫检查点
免疫系统
免疫学
干细胞
细胞生物学
癌症
免疫疗法
头颈部癌
遗传学
作者
Cheng Wang,Yang Li,Lingfei Jia,Jin Koo Kim,Jiong Li,Peng Deng,Wuchang Zhang,Paul H. Krebsbach,Cun‐Yu Wang
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2021-09-01
卷期号:28 (9): 1597-1613.e7
被引量:137
标识
DOI:10.1016/j.stem.2021.04.011
摘要
Immunosurveillance is a critical mechanism guarding against tumor development and progression. Checkpoint inhibitors have shown significant success in cancer treatment, but expression of key factors such as PD-L1 in putative cancer stem cell (CSC) populations in squamous cell carcinoma has been inconclusive, suggesting that CSCs may have developed other mechanisms to escape immune surveillance. Here we show that CSCs upregulate the immune checkpoint molecule CD276 (B7-H3) to evade host immune responses. CD276 is highly expressed by CSCs in mouse and human head and neck squamous cell carcinoma (HNSCC) and can be used to prospectively isolate tumorigenic CSCs. Anti-CD276 antibodies eliminate CSCs in a CD8+ T cell-dependent manner, inhibiting tumor growth and lymph node metastases in a mouse HNSCC model. Single-cell RNA sequencing (RNA-seq) showed that CD276 blockade remodels SCC heterogeneity and reduces epithelial-mesenchymal transition. These results show that CSCs utilize CD276 for immune escape and suggest that targeting CD276 may reduce CSCs in HNSCC.
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