PVT1 inhibition stimulates anti-tumor immunity, prevents metastasis, and depletes cancer stem cells in squamous cell carcinoma

Abstract

AbstractCancer stem cells (CSCs) cause tumor metastasis and immune evasion by as-yet-unknown 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 lymph 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 cell-recruiting chemokines, while preventing 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.