Affiliation:
1. Peking University School and Hospital of Stomatology
2. Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
Abstract
Abstract
Cancer stem cells (CSCs) cause tumor metastasis and immune evasion by asyetunknown molecular mechanisms. In the present study, we identify a long noncoding RNA (lncRNA), termed PVT1, which is highly expressed in CSCs and correlated closely with lymphoma node metastasis of head and neck squamous cell carcinoma (HNSCC). PVT1 inhibition eliminates CSCs, prevents metastasis, and stimulates anti-tumor immunity, while inhibiting HNSCC growth. Moreover, PVT1 inhibition promotes the infiltration of CD8+ T cells into the tumor microenvironment, thereby enhancing immunotherapy by PD1 blockade. Mechanistically, PVT1 inhibition stimulates the DNA damage response, which induces CD8+ T cellrecruiting chemokines, while reducing CSCs and metastasis via regulating the miR-375/YAP1 axis. In conclusion, targeting PVT1 might potentiate the elimination of CSCs via immune checkpoint blockade, prevent metastasis, and inhibit HNSCC growth.
Publisher
Research Square Platform LLC